rs200050883

Variant names:

• chr22-28695190-C-A
• rs200050883
• NM_007194.4:c.1312G>T

Your query was ambiguous. Multiple possible variants found:

• chr22-28695190-C-A
• chr22-28695190-C-G
• chr22-28695190-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6 BS2_Supporting

The NM_007194.4(CHEK2):​c.1312G>T​(p.Asp438Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000376 in 1,613,498 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00037 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00038 (2 hom.)
• Consequence: CHEK2 NM_007194.4 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:21 B:11 O:2
• Conservation: PhyloP100: 4.62

Genes affected

CHEK2 (HGNC:16627): (checkpoint kinase 2) In response to DNA damage and replication blocks, cell cycle progression is halted through the control of critical cell cycle regulators. The protein encoded by this gene is a cell cycle checkpoint regulator and putative tumor suppressor. It contains a forkhead-associated protein interaction domain essential for activation in response to DNA damage and is rapidly phosphorylated in response to replication blocks and DNA damage. When activated, the encoded protein is known to inhibit CDC25C phosphatase, preventing entry into mitosis, and has been shown to stabilize the tumor suppressor protein p53, leading to cell cycle arrest in G1. In addition, this protein interacts with and phosphorylates BRCA1, allowing BRCA1 to restore survival after DNA damage. Mutations in this gene have been linked with Li-Fraumeni syndrome, a highly penetrant familial cancer phenotype usually associated with inherited mutations in TP53. Also, mutations in this gene are thought to confer a predisposition to sarcomas, breast cancer, and brain tumors. This nuclear protein is a member of the CDS1 subfamily of serine/threonine protein kinases. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.045587093).
• BP6: Variant 22-28695190-C-A is Benign according to our data. Variant chr22-28695190-C-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 128056.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=9, Uncertain_significance=13, not_provided=2}.
• BS2: High Homozygotes in GnomAdExome4 at 2 AD,AR geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHEK2	NM_007194.4	c.1312G>T	p.Asp438Tyr	missense_variant	Exon 12 of 15	ENST00000404276.6	NP_009125.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHEK2	ENST00000404276.6	c.1312G>T	p.Asp438Tyr	missense_variant	Exon 12 of 15	1	NM_007194.4	ENSP00000385747.1

Frequencies

GnomAD3 genomes AF: 0.000375 AC: 57 AN: 152144 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000966

Gnomad AMI AF: 0.00549

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.000754

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000514

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000386 AC: 97 AN: 251038 Hom.: 0 AF XY: 0.000339 AC XY: 46 AN XY: 135660

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000294

Gnomad FIN exome AF: 0.00134

Gnomad NFE exome AF: 0.000459

Gnomad OTH exome AF: 0.000490

GnomAD4 exome AF: 0.000376 AC: 549 AN: 1461236 Hom.: 2 Cov.: 30 AF XY: 0.000359 AC XY: 261 AN XY: 726952

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.000112

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000394

Gnomad4 FIN exome AF: 0.00131

Gnomad4 NFE exome AF: 0.000362

Gnomad4 OTH exome AF: 0.000265

GnomAD4 genome AF: 0.000374 AC: 57 AN: 152262 Hom.: 1 Cov.: 32 AF XY: 0.000403 AC XY: 30 AN XY: 74442

Gnomad4 AFR AF: 0.0000963

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.000754

Gnomad4 NFE AF: 0.000514

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000426 Hom.: 1

Bravo AF: 0.000280

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000280 AC: 34

EpiCase AF: 0.00109

EpiControl AF: 0.000593

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:21 Benign:11 Other:2

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Uncertain:9 Benign:2 Other:1

Sep 01, 2023

Quest Diagnostics Nichols Institute San Juan Capistrano

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

In the published literature, this variant has been reported in individuals with breast cancer (PMIDs: 36653541 (2023), 35886069 (2022), 33558524 (2021), 33134171 (2020), 31050813 (2019), 29484706 (2018), 29335925 (2018), 28779002 (2017), 25186627 (2015), 24390236 (2014), 21244692 (2011)), endometrial cancer (PMID:27443514 (2016)), colorectal cancer (PMID: 29987844 (2018)), and prostate cancer (PMIDs: 18571837 (2008), 17721994 (2007), 14612911 (2003)). This variant has also been identified in healthy control individuals (PMIDs: 36653541 (2023), 31050813 (2019), 30303537 (2019), 28779002 (2017), 21244692 (2011), 17721994 (2007)), and reported to co-occur with deleterious variants in the MRE11 and MSH2 genes (PMIDs: 33134171 (2020), 27443514 (2016)). Case-control studies suggest this variant is associated with prostate cancer risk but not breast cancer risk (PMIDs: 27595995 (2016), 36653541 (2023)). In addition, experimental studies indicate this variant has neutral to intermediate effects on CHEK2 protein function (PMIDs: 34903604 (2022), 31050813 (2019), 30851065 (2019), 17721994 (2007)). The frequency of this variant in the general population, 0.0013 (32/25122 chromosomes in European (Finnish) subpopulation (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is higher than would generally be expected for pathogenic variants in this gene. Based on the available information, we are unable to determine the clinical significance of this variant. -

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Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

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GenomeConnect, ClinGen

Significance: not provided

Review Status: no classification provided

Collection Method: phenotyping only

The variant was identified in multiple GenomeConnect participants. Variant interpreted as Uncertain significance and reported on 03-29-2018 by Lab or GTR ID Northwell Health Laboratories. Variant interpreted as Uncertain significance and reported, most recently, on 12/04/2018 by GTR ID Credit Valley Hospital Department of Laboratory Medicine. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. -

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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

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Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Nov 03, 2021

Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

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Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Apr 26, 2023

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Published functional studies are inconclusive/conflicting: demonstrates intermediate/reduced kinase activity in some studies while others, including a human-cell based assay, show activity comparable to wildtype (Bell et al., 2007; Delimitsou et al., 2019; Kleiblova et al., 2019; Boonen et al., 2022); Observed in individuals with a personal and/or family history of breast, prostate, or colorectal cancer (Seppala et al., 2003; Bell et al., 2007; Tischkowitz et al., 2008; Baloch et al., 2014; Tung et al., 2015; Kayser et al., 2018; Fanale et al., 2020; Grasel et al., 2020; Moradian et al., 2021; Paduano et al., 2022); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 14612911, 15087378, 28828701, 28776603, 28873162, 24390236, 17721994, 18571837, 23960188, 21244692, 27067391, 26787654, 28553140, 25186627, 27153395, 27498913, 27878467, 28452373, 19768534, 29335925, 27595995, 27443514, 29987844, 29484706, 30344923, 28301460, 30851065, 29875428, 29522266, 31050813, 31398194, 31159747, 28779002, 31220302, 33134171, 33322746, 32854451, 33558524, 27009842, 32906215, 30613976, 27535533, 34903604, 34347074, 22419737, 19782031, 35886069, 33840814) -

Jun 14, 2023

Revvity Omics, Revvity

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CHEK2: BP4, BS2 -

Familial cancer of breast Uncertain:2 Benign:3

Mar 09, 2023

Myriad Genetics, Inc.

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign. This variant is strongly associated with less severe personal and family histories of cancer, typical for individuals without pathogenic variants in this gene [PMID: 25085752]. -

Apr 08, 2020

Center of Medical Genetics and Primary Health Care

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: research

ACMG Guidelines 2015 criteria PM1 Pathogenic Moderate: Pkinase domain (M265-529L aa) which contains the catalytic function of protein kinases. Hot-spot has 21 non-VUS coding variants (7 pathogenic and 14 benign), pathogenicity = 33.3%, proximity score 3.967 > threshold 2.472. PP1 Pathogenic Supporting: Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease. PP2 Pathogenic Supporting: 30 out of 48 non-VUS missense variants in gene CHEK2 are pathogenic = 62.5% > threshold of 51.0%, and 308 out of 1,604 clinically reported variants in gene CHEK2 are pathogenic = 19.2% > threshold of 12.0%. PP1 Pathogenic Supporting: 2 patients are sibs (sisters) who share the same variant. BP4 Benign Supporting: 6 benign predictions from DEOGEN2, EIGEN, MVP, MutationAssessor, PrimateAI and REVEL vs 5 pathogenic predictions from DANN, FATHMM-MKL, M-CAP, MutationTaster and SIFT and the position is not conserved." Therefore, this variant was classified as a Variant of Unknown Significance. -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Nov 22, 2022

Research Unit of Translational Medicine, University of Oulu

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: research

The frequency of p.Asp438Tyr variant in CHEK2 among Northern Finnish breast cancer cases was 0.6% (14/2284) and nearly equal in geographically matched healthy population controls (0.8%, 10/1299) in a study by Kumpula et al. (2023). Similar carrier frequencies in the studied cases and the general population argue against association of CHEK2 p.Asp438Tyr with increased breast cancer risk. Therefore the variant can be classified as likely benign. -

Aug 12, 2016

Counsyl

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hereditary cancer-predisposing syndrome Uncertain:2 Benign:2

Aug 30, 2019

Color Diagnostics, LLC DBA Color Health

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Aug 01, 2018

GeneKor MSA

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Department of Pediatric Oncology, Hematology and Clinical Immunology, University Clinics Duesseldorf

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: research

- -

Dec 14, 2020

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not specified Uncertain:2 Benign:1

Aug 28, 2023

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant summary: CHEK2 c.1312G>T (p.Asp438Tyr) results in a non-conservative amino acid change located in the Protein kinase domain (IPR000719) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0004 in 261860 control chromosomes, predominantly at a frequency of 0.00046 within the Non-Finnish European subpopulation in the gnomAD database. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 1.5- fold the estimated maximal expected allele frequency for a pathogenic variant in CHEK2 causing Hereditary Breast and Ovarian Cancer phenotype (0.00031), suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. However, the frequency in gnomAD and the cases reported in the literature may not be accurate due to the sequencing technology used being unable to distinguish between CHEK2 and its multiple overlapping pseudogenes. This variant has also been reported among 7 women older than 70 years who have never had cancer as reported in the FLOSSIES database. c.1312G>T, has been reported in the literature in individuals affected with Breast and/or Ovarian Cancer, but also in controls and in a family where it did not segregate with disease (examples- Baloch_2013, Bell_2007, LeCalvez-Kelm_2011, Seppala_2003, Tischkowitz_2008, Young_2016, Yadav_2016, Tung_2015, Maxwell_2016, Fostira_2018, Scarpetta_2019). Case control approaches indicated no significant risk association for breast cancer, but a slightly elevated risk for prostate cancer (Le Calvez-Kelm_2011, Southey_2016). These data thus do not allow any conclusion about variant significance. At-least one co-occurrence with another pathogenic variant has been reported (MSH2 c.1697del, p.Asn566IlefsX24), providing supporting evidence for a benign role (Ring_2016). In a mammalian cell based kinase-assay the variant protein showed about 70% reduction in activity (Bell_2007), whereas in a yeast based DNA-damage assay the variant showed similar function to the wild type supporting a benign outcome (Delimitsou_2019). The following publications have been ascertained in the context of this evaluation (PMID: 24390236, 17721994, 15087378, 30851065, 31811167, 29335925, 30303537, 33134171, 29484706, 25231023, 29987844, 21244692, 30322893, 27153395, 33558524, 27443514, 31512090, 14612911, 27595995, 18571837, 31159747, 25186627, 29875428, 27878467, 31214250, 26787654, 28828701, 23960188). Multiple clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and cited the variant as uncertain significance (n=15) and likely benign (n=5). Based on the evidence outlined above, the variant was classified as likely benign. -

Jan 11, 2019

Genetic Services Laboratory, University of Chicago

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

CHEK2-related cancer predisposition Uncertain:1 Other:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -

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GenomeConnect - Invitae Patient Insights Network

Significance: not provided

Review Status: no classification provided

Collection Method: phenotyping only

Variant interpreted as Likely benign and reported on 04-04-2017 by Lab Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. -

Breast and/or ovarian cancer Uncertain:1

Feb 27, 2023

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Familial cancer of breast;C0376358:Malignant tumor of prostate;C0585442:Bone osteosarcoma;C5882668:Li-Fraumeni syndrome 2 Uncertain:1

May 23, 2017

Fulgent Genetics, Fulgent Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Hereditary breast ovarian cancer syndrome Uncertain:1

Jan 09, 2024

German Consortium for Hereditary Breast and Ovarian Cancer, University Hospital Cologne

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: curation

Results from functional assays as well as predictions are contradictory. According to the ACMG standard criteria we chose this criterium: BS1 (strong benign): gnomAD v3.1.2 (non-cancer): AF: 0.0005092 + 1 x hom -

Li-Fraumeni syndrome 2 Uncertain:1

Oct 12, 2019

Baylor Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. -

Carcinoma of colon Uncertain:1

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Department of Pathology and Laboratory Medicine, Sinai Health System

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

The CHEK2 p.Asp438Tyr variant was identified in 4 of 1332 proband chromosomes (frequency: 0.003) from Pakistani, Finnish, Polish and Ashkenazi Jewish individuals or families with breast, early onset breast and prostate, or hereditary prostate cancer and was not identified in 590 control chromosomes from healthy individuals (Baloch 2014, Seppala 2003, Tischkowitz 2008, Bell 2007). The variant was identified in dbSNP (ID: rs200050883) “With Uncertain significance allele”, ClinVar (classified as uncertain significance by GeneDx, Ambry Genetics, Invitae, Counsyl, and Color Genomics), and the Zhejiang Colon Cancer Database (14x, co-occurring with CHEK2 c.1100delC). The variant was not identified in Cosmic. The variant was identified in control databases in 108 of 276806 chromosomes at a frequency of 0.0004 (Genome Aggregation Consortium Feb 27, 2017). The variant was identified in the following populations: European in 57 of 126326 chromosomes (frequency: 0.0005), Finnish in 33 of 25792 chromosomes (frequency: 0.001), African in 3 of 24032 chromosomes (frequency: 0.0001), Other in 4 of 6456 chromosomes (frequency: 0.0006), Latino in 2 of 34404 chromosomes (frequency: 0.00006), and South Asian in 9 of 30776 chromosomes (frequency: 0.0003). The variant occurs in the catalytic domain of the CHEK2 protein and in vitro analysis of kinase activity showed the variant had a 70% decrease in activity compared to wildtype (Baloch 2014, Bell 2007). The p.Asp438 residue is conserved in mammals but not in more distantly related organisms, and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) suggest that the Tyr variant may impact the protein; however, this information is not predictive enough to assume pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. -

CHEK2-related disorder Benign:1

Aug 28, 2024

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Hereditary cancer Benign:1

Jan 23, 2024

Mendelics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Malignant tumor of breast Benign:1

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Center of Medical Genetics and Primary Health Care

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.084	T
BayesDel_noAF	Uncertain	-0.010
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T;.;T;.;T;.;T;.;.
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.93	.;D;.;D;.;D;D;D;.
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.046	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.3	L;.;L;.;L;.;L;.;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-4.9	D;D;D;.;D;D;.;D;D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0020	D;D;D;.;D;D;.;D;D
Sift4G	Uncertain	0.0070	D;D;D;.;D;D;.;D;D
Polyphen		1.0	D;D;D;.;D;P;D;D;D
Vest4		0.74
MVP		0.83
MPC		0.15
ClinPred		0.16	T
GERP RS		5.8
Varity_R		0.82
gMVP		0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs200050883; hg19: chr22-29091178; COSMIC: COSV105248010; COSMIC: COSV105248010;