chr22-28696960-G-A

Variant names:

• chr22-28696960-G-A
• rs201206424
• NM_007194.4:c.1036C>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 5P and 1B. PM5 PP3_Moderate PP5 BS2_Supporting

The NM_007194.4(CHEK2):​c.1036C>T​(p.Arg346Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000446 in 1,612,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R346H) has been classified as Likely pathogenic.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000049 (0 hom.)
• Consequence: CHEK2 NM_007194.4 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:8 U:17
• Conservation: PhyloP100: 2.78
• Publications: 41 publications found

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]

CHEK2 Gene-Disease associations (from GenCC):

• CHEK2-related cancer predisposition

  Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics
• hereditary breast carcinoma

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
• Li-Fraumeni syndrome 2

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
• acute myeloid leukemia

  Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
• hereditary nonpolyposis colon cancer

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• familial ovarian cancer

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM5: Other missense variant is known to change same aminoacid residue: Variant chr22-28696959-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 182431.
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.912
• PP5: Variant 22-28696960-G-A is Pathogenic according to our data. Variant chr22-28696960-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 142222.
• BS2: High AC in GnomAdExome4 at 71 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007194.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHEK2	NM_007194.4	MANE Select	c.1036C>T	p.Arg346Cys	missense	Exon 10 of 15	NP_009125.1
	CHEK2	NM_001005735.3		c.1165C>T	p.Arg389Cys	missense	Exon 11 of 16	NP_001005735.1
	CHEK2	NM_001438293.1		c.1129C>T	p.Arg377Cys	missense	Exon 11 of 16	NP_001425222.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHEK2	ENST00000404276.6	TSL:1 MANE Select	c.1036C>T	p.Arg346Cys	missense	Exon 10 of 15	ENSP00000385747.1
	CHEK2	ENST00000382580.6	TSL:1	c.1165C>T	p.Arg389Cys	missense	Exon 11 of 16	ENSP00000372023.2
	CHEK2	ENST00000402731.6	TSL:1	c.835C>T	p.Arg279Cys	missense	Exon 8 of 13	ENSP00000384835.2

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152032 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000517 AC: 13 AN: 251222 AF XY: 0.0000589

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000880

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000486 AC: 71 AN: 1460714 Hom.: 0 Cov.: 29 AF XY: 0.0000495 AC XY: 36 AN XY: 726734

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39676

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86220

European-Finnish (FIN) AF: 0.0000375 AC: 2 AN: 53354

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000549 AC: 61 AN: 1111032

Other (OTH) AF: 0.0000828 AC: 5 AN: 60354

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152032 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74258

African (AFR) AF: 0.00 AC: 0 AN: 41402

American (AMR) AF: 0.0000656 AC: 1 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10566

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000697 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.0000412 AC: 5

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:8 Uncertain:17

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Familial cancer of breast Pathogenic:2 Uncertain:5

Jan 22, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 346 of the CHEK2 protein (p.Arg346Cys). This variant is present in population databases (rs201206424, gnomAD 0.009%). This missense change has been observed in individual(s) with breast cancer (PMID: 21244692, 27595995, 30651582, 30851065, 33128190). ClinVar contains an entry for this variant (Variation ID: 142222). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on CHEK2 function (PMID: 30851065, 36468172). RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (internal data). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

Jun 20, 2024

Molecular Pathology, Peter Maccallum Cancer Centre

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Feb 12, 2025

Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Feb 02, 2018

Counsyl

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com.

Oct 25, 2024

Myriad Genetics, Inc.

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely pathogenic. Functional studies indicate this variant impacts protein function [PMID: 37449874]. This variant is strongly associated with more severe personal and family histories of cancer, typical for individuals with pathogenic variants in this gene [PMID: 25085752].

Oct 30, 2023

Baylor Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Jul 02, 2018

Mendelics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Pathogenic:2 Uncertain:3

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CHEK2: PS4:Moderate, PM2:Supporting, PS3:Supporting

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Likely pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

May 19, 2023

Revvity Omics, Revvity

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Jan 16, 2025

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Case control studies suggest this variant may be associated with breast cancer (PMID: 21244692, 27595995); Observed in individuals with breast or ovarian cancer (PMID: 30130155, 30303537, 30651582, 33925588, 34326862, 34204722, 33128190, 35264596); This variant is associated with the following publications: (PMID: 21244692, 26787654, 22114986, 28452373, 30287823, 31050813, 28580595, 30651582, 30303537, 33128190, 34204722, 33925588, 33134171, 33471991, 30975761, 36315097, 34326862, 30130155, 36978154, 36243179, 35264596, 27595995, 35441217, 35534704, 35493704, 35980532, 37449874, 22419737, 19782031, 36468172, 39146382, 30851065)

Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute

Significance: Likely pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

Hereditary cancer-predisposing syndrome Pathogenic:2 Uncertain:2

Mar 20, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The p.R346C variant (also known as c.1036C>T), located in coding exon 9 of the CHEK2 gene, results from a C to T substitution at nucleotide position 1036. The arginine at codon 346 is replaced by cysteine, an amino acid with highly dissimilar properties. In a study involving 42671 cases and 42164 controls, this variant was significantly associated with breast cancer [OR 5.06 (95% CI 1.09 to 23.5); p=0.017] (Southey MC et al. J. Med. Genet. 2016 Dec;53:800-811). In another study, this variant did not segregate with cancer in one family, but did show loss of heterozygosity in a tumor specimen (Grasel RS et al. Front Oncol, 2020 Oct;10:571330). This alteration has been identified in individuals diagnosed with breast cancer, ovarian cancer and mesothelioma (Le Calvez-Kelm F et al. Breast Cancer Res. 2011 Jan;13:R6; Zheng Y et al. J Clin Oncol, 2018 Oct;36:2820-2825; Girard E et al. Int. J. Cancer, 2019 04;144:1962-1974; Hassan R et al. Proc Natl Acad Sci U S A, 2019 04;116:9008-9013; Krivokuca A et al. J. Hum. Genet., 2019 Apr;64:281-290; Apostolou P et al. Cancers (Basel), 2021 Apr;13:; Gomes R et al. Breast Cancer Res Treat, 2021 Feb;185:851-861). Protein functional studies has demonstrated this variant to be deleterious (Delimitsou A et al. Hum. Mutat., 2019 05;40:631-648; Stolarova L et al. Clin Cancer Res 2023 Aug;29(16):3037-3050). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear.

Jul 15, 2025

Molecular Diagnostics Laboratory, Catalan Institute of Oncology

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PS3_Moderate, PS4, PM1, PM2_Supporting c.1036C>T, located in exon 10 of the CHEK2 gene, is predicted to result in the substitution of Arg by Cys at codon 346, p.(Arg346Cys). This variant affects a highly conserved amino acid of the kinase-domain (226-486 aa) (PM1). This variant is found in 10/268119 alleles at a frequency of 0.0037% in the gnomAD v2.1.1 database, non-cancer dataset (PM2_Supporting). The SpliceAI algorithm predicts no significant impact on splicing and the REVEL meta-predictor score for this variant (0.78) suggests a deleterious effect on protein function according to Pejaver 2022 thresholds (PMID: 36413997). Functional studies (kinase activity in human cells and DNA-damage response in yeast cells) have shown that this variant has a damaging effect (PMID: 30851065, 37449874) (PS3_Moderate). This variant has been associated with breast cancer risk, in at leat to case-control studies, resulting in OR: 5.06 (CI: 1.09-23) (PMID: 27595995) and OR: 5.85 (CI: 2.00-16.92) (PMID: 37449874) (PS4). It has been reported in ClinVar (7x likely pathogenic, 15x uncertain significance) and LOVD (3x likely pathogenic, 1x uncertain significance) databases. Based on the currently available evidence, c.1036C>T should be considered a likely pathogenic variant according to ACMG/AMP classification guidelines.

Nov 04, 2024

Color Diagnostics, LLC DBA Color Health

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This missense variant replaces arginine with cysteine at codon 346 in the kinase domain of the CHEK2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function. A functional study in human cells has shown the mutant protein to be defective in KAP1 phosphorylation and CHEK2 autophosphorylation (PMID: 37449874) and a study in yeast has shown the mutant protein to be defective in DNA damage response (PMID: 30851065). This variant has been reported in several large breast cancer case-control studies or meta-analyses, achieving a statistically significant association with breast cancer in the largest of these studies (23/73048 cases and 4/88658 unaffected controls (OR=5.85, 95% CI 2.00-16.92) (PMID: 37449874). These findings are consistent with a risk comparable to pathogenic truncating variants and certain pathogenic missense variants in CHEK2, such as p.Arg117Gly which has been reported to have an association with breast cancer (OR 2.38, 95% CI 1.59-3.57; PMID: 37490054, 37449874). The other smaller studies showed similar association but had not yet achieved statistical significance (10/60466 cases and 2/53461 unaffected controls (OR=4.421, 95% CI 0.969-20.18) (PMID: 33471991; Leiden Open Variation Database DB-ID CHEK2_00011), 9/42671 cases and 2/42164 unaffected controls (OR=5.06. 95% CI 1.09-23.5) (PMID: 27595995), and 3/1313 cases and 0/1123 unaffected controls (OR=5.91, 95% CI 0.3051 to 114.5995) (PMID: 21244692). This variant has been identified in 13/251222 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Likely Pathogenic.

Dec 17, 2021

Sema4, Sema4

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: curation

Hereditary breast ovarian cancer syndrome Pathogenic:1 Uncertain:1

Aug 01, 2020

Molecular Oncology Research Center, Barretos Cancer Hospital

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: research

Feb 11, 2025

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

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: curation

According to the ACMG SVI adaptation criteria we chose these criteria: PS3 (strong pathogenic): Delimitsou, 2019 (PMID: 30851065): Damaging, Stolarova, 2023 (PMID: 37449874): functionally impaired, PS4 (medium pathogenic): OR 5.06 (95% CI 1.09 to 23.5); p=0.017] (Southey MC et al. J. Med. Genet. 2016 Dec;53:800-811), PP3 (supporting pathogenic): REVEL 0,78

not specified Uncertain:2

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Apr 26, 2024

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

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant summary: CHEK2 c.1036C>T (p.Arg346Cys) 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 5.2e-05 in 251222 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in CHEK2 causing Prostate Cancer (5.2e-05 vs 0.00025), allowing no conclusion about variant significance. c.1036C>T has been reported in the literature in individuals affected with various types of Cancer, including Breast cancer, Biliary tract cancer, Langer Hans Cell Histiocytosis and B-cell acute lymphoblastic leukemia (example, Guindalini_2022, Bhai_2021, Wagener_2022, Pereira_2022), and was also reported in the control cohorts from at-least two large case-control studies of cancer risk (example, Dorling_2021, Okawa_2023). These report(s) do not provide unequivocal conclusions about association of the variant with Prostate Cancer and other CHEK2-related conditions. At least two publications report experimental evidence evaluating an impact on protein function. In a yeast growing assay, this variant significantly inhibit the normal growth of yeast (Delimitsou_2019), however in a subsequent study using an osteosarcoma cell line, this variant did not affect CHK2 function, as it resulted in comparable/slightly increased CHEK2 levels and was able to induce Phosphorylation of CHK2-Thr68 (Wagener_2022). The following publications have been ascertained in the context of this evaluation (PMID: 34326862, 30851065, 33471991, 35264596, 36243179, 35980532, 36468172). ClinVar contains an entry for this variant (Variation ID: 142222). Based on the evidence outlined above, the variant was classified as uncertain significance.

CHEK2-related cancer predisposition Pathogenic:1

May 26, 2025

Institute of Human Genetics, University of Leipzig Medical Center

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Criteria applied: PS3,PS4_MOD,PP3

Breast-ovarian cancer, familial, susceptibility to, 1 Uncertain:1

Jul 30, 2025

Institute of Immunology and Genetics Kaiserslautern

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ACMG Criteria: PS3_P, PM1, PP3 ; Variant was found in heterozygous state.

Breast and/or ovarian cancer Uncertain:1

Feb 07, 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:Prostate cancer;C0585442:Bone osteosarcoma;C5882668:CHEK2-related cancer predisposition Uncertain:1

Oct 31, 2018

Fulgent Genetics, Fulgent Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Malignant tumor of breast Uncertain:1

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.Arg346Cys variant was identified in 3 of 2606 proband chromosomes (frequency: 0.001) from individuals or families with breast cancer (Le Calvez-Kelm 2011). The variant was also identified in dbSNP (ID: rs201206424) as "With Uncertain significance allele", ClinVar (classified as uncertain significance by Ambry Genetics, GeneDx, Invitae, Color Genomics, and Counsyl), and Cosmic (3x in breast, large intestine or lung tissue); it was not identified in MutDB or the Zhejiang University database. The variant was identified in control databases in 13 of 246016 chromosomes at a frequency of 0.00005 (Genome Aggregation Database Feb 27, 2017) in the following populations: European in 10 of 111540 chromosomes (freq: 0.00009), Other in 1 of 5472 chromosomes (freq: 0.0002), East Asian in 1 of 17248 chromosomes (freq: 0.00006), and South Asian in 1 of 30776 chromosomes (freq: 0.00003); it was not observed in the African, Latino, Ashkenazi Jewish, or Finnish populations. The p.Arg346 residue is conserved across mammals and other organisms and 5 of 5 computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) suggest that the 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.

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Pathogenic	0.27
CADD	Pathogenic	31
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.38	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Pathogenic	0.30	D
MetaRNN	Pathogenic	0.91	D
MetaSVM	Uncertain	-0.044	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		2.8
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-7.5	D
REVEL	Pathogenic	0.78
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.98
MVP		0.78
MPC		0.18
ClinPred		0.99	D
GERP RS		3.5
Varity_R		0.92
gMVP		0.85
Mutation Taster		=21/79	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		2.0
SpliceAI score (max)		0.11		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs201206424; hg19: chr22-29092948; COSMIC: COSV60422106; COSMIC: COSV60422106;