11-108335105-T-C

Position:

chr11-108335105-T-C

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PP3_StrongPP5_Very_Strong

The NM_000051.4(ATM):c.8147T>C(p.Val2716Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000273 in 1,613,980 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 Likely pathogenic (★★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

ATM
NM_000051.4 missense

Scores

Clinical Significance

Pathogenic/Likely pathogenic criteria provided, multiple submitters, no conflicts P:40O:1

Conservation

PhyloP100: 7.63

Variant links:

Genes affected

ATM (HGNC:795): (ATM serine/threonine kinase) The protein encoded by this gene belongs to the PI3/PI4-kinase family. This protein is an important cell cycle checkpoint kinase that phosphorylates; thus, it functions as a regulator of a wide variety of downstream proteins, including tumor suppressor proteins p53 and BRCA1, checkpoint kinase CHK2, checkpoint proteins RAD17 and RAD9, and DNA repair protein NBS1. This protein and the closely related kinase ATR are thought to be master controllers of cell cycle checkpoint signaling pathways that are required for cell response to DNA damage and for genome stability. Mutations in this gene are associated with ataxia telangiectasia, an autosomal recessive disorder. [provided by RefSeq, Aug 2010]

ATM links:

C11orf65 (HGNC:28519): (chromosome 11 open reading frame 65) Predicted to be involved in negative regulation of mitochondrial fission and negative regulation of protein targeting to mitochondrion. Predicted to be located in cytosol and mitochondrial outer membrane. [provided by Alliance of Genome Resources, Apr 2022]

C11orf65 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 12 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.959

PP5

Variant 11-108335105-T-C is Pathogenic according to our data. Variant chr11-108335105-T-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 142700.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-108335105-T-C is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATM	NM_000051.4 linkuse as main transcript	c.8147T>C	p.Val2716Ala	missense_variant	55/63	ENST00000675843.1	NP_000042.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATM	ENST00000675843.1 linkuse as main transcript	c.8147T>C	p.Val2716Ala	missense_variant	55/63		NM_000051.4	ENSP00000501606	P1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000318

AC:

AN:

251342

Hom.:

AF XY:

0.0000294

AC XY:

AN XY:

135850

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.0000616

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000253

AC:

AN:

1461762

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

727176

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000324

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000980

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Pathogenic/Likely pathogenic

Submissions summary: Pathogenic:40Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Ataxia-telangiectasia syndrome

Pathogenic:11Other:1

Pathogenic, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 02, 2023	The p.Val2716Ala variant in ATM has been reported in >20 compound heterozygous individuals with ataxia telangectasia and segregated with disease in 3 affected individuals from 2 families. Most of these cases, however are atypical and mild cases of ataxia telangectasia (Verhagen 2009 PMID: 19535770, van Os 2019 PMID: 30819809, Schon 2019 PMID: 30549301, Lohmann 2015 PMID: 25957637, Fievet 2019 PMID: 31050087, Heil 2006 PMID: 16864838, Demuth 2011 PMID: 21965147, Reiman 2011 PMID: 21792198). It has also been found in individuals with breast cancer (Reiman 2011 PMID: 21792198, Mandigers 2011 PMID: 21354641, Fanale 2020 PMID: 32854451, Susswein 2016 PMID: 26681312). It has also been identified in 0.0088% (6/68034) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org). This variant has also been reported in ClinVar (Variation ID 142700). Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In vitro functional studies provide some evidence that this variant reduces, however retains some protein function, which may produce the more mild symptoms seen in patients (Scott 2002 PMID: 11805335, Demuth 2011 PMID: 21965147). In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive ataxia telangectasia, though presentation may be atypical. ACMG/AMP Criteria applied: PM3_Very Strong, PP1_Strong, PS3_Moderate, PM2_Supporting, PP3. -
Pathogenic, criteria provided, single submitter	not provided	Institute for Medical Genetics and Human Genetics, Charité - Universitätsmedizin Berlin	-	- -
Pathogenic, criteria provided, single submitter	clinical testing	Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München	Jan 10, 2018	- -
Pathogenic, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 2716 of the ATM protein (p.Val2716Ala). This variant is present in population databases (rs587782652, gnomAD 0.005%). This missense change has been observed in individual(s) with ataxia-telangiectasia (A-T), generalized dystonia, breast cancer, and dystonia (PMID: 2557216, 16864838, 19535770, 21354641, 21965147, 25957637, 26976419). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 142700). 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 have shown that this missense change affects ATM function (PMID: 11805335). For these reasons, this variant has been classified as Pathogenic. -
Likely pathogenic, criteria provided, single submitter	literature only	Counsyl	May 13, 2014	- -
Likely pathogenic, criteria provided, single submitter	clinical testing	Revvity Omics, Revvity	Sep 08, 2019	- -
Pathogenic, criteria provided, single submitter	research	Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Fondazione Stella Maris	Jan 04, 2021	- -
not provided, no classification provided	literature only	GeneReviews	-	- -
Pathogenic, criteria provided, single submitter	clinical testing	KCCC/NGS Laboratory, Kuwait Cancer Control Center	May 31, 2023	The ATM family pathogenic mutation was detected in this specimen as heterozygous .The mutation detected in the son segregated with this finding .This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 2716 of the ATM protein (p.Val2716Ala). This variant is present in population databases (rs587782652, gnomAD 0.005%).This amino acid position is highly conserved. This missense change has been observed in individual(s) with ataxia-telangiectasia (A-T), generalized dystonia, breast cancer, and dystonia (PMID: 2557216, 16864838, 19535770, 21354641, 21965147, 25957637, 26976419) and others . ClinVar contains an entry for this variant (Variation ID: 142700) classified as Pathogenic/Likely pathogenic by multiples submitters . In silico analysis supports that this missense variant has a deleterious effect on protein structure/function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects ATM function (PMID: 11805335). For these reasons, this variant has been classified as Pathogenic. Homozygous or compound pathogenic/likely pathogenic mutations in the ATM gene are known to cause Ataxia- Telangiectasia. Heterozygous pathogenic/likely pathogenic mutations in the ATM gene are associated with increased risk of certain cancers. -
Likely pathogenic, criteria provided, single submitter	clinical testing	3billion	Feb 23, 2023	The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.003%). Protein truncation variants are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.91; 3Cnet: 0.74). Same nucleotide change resulting in same amino acid change (ClinVar ID: VCV000142700) and a different missense change at the same codon (p.Val2716Phe / ClinVar ID: VCV000181985) have been previously reported as pathogenic/likely pathogenic with strong evidence. Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline. -
Pathogenic, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Sep 10, 2018	Variant summary: ATM c.8147T>C (p.Val2716Ala) results in a non-conservative amino acid change located in the Phosphatidylinositol 3-/4-kinase, catalytic domain 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 3.2e-05 in 277104 control chromosomes (gnomAD). The variant, c.8147T>C, has been reported in the literature in multiple individuals affected with Ataxia-Telangiectasia (Demuth_2011, Hiel_2006, Lohmann_2015). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal activity (Scott_2001). Five ClinVar submission from other clinical diagnostic laboratories (evaluation after 2014) cite the variant as likely pathogenic/pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. -
Pathogenic, criteria provided, single submitter	curation	Laboratory of Medical Genetics, National & Kapodistrian University of Athens	Feb 01, 2024	- -

not provided

Pathogenic:10

Pathogenic, criteria provided, single submitter	clinical testing	Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	Nov 03, 2021	- -
Pathogenic, no assertion criteria provided	clinical testing	Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	-	- -
Pathogenic, criteria provided, single submitter	clinical testing	Athena Diagnostics	Dec 20, 2022	The frequency of this variant in the general population is consistent with pathogenicity (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org)). This variant segregates with ataxia-telangiectasia in at least one family. Assessment of experimental evidence suggests this variant results in abnormal protein function. (PMID: 11805335) In multiple individuals, this variant has been seen with a single recessive pathogenic variant in the same gene, suggesting this variant may also be pathogenic. -
Pathogenic, criteria provided, single submitter	clinical testing	GeneDx	Jul 29, 2022	Published functional studies support a damaging effect: expresses some level of kinase activity, but shows reduced ATM protein expression and transfected cells have exhibited reduced radiation-induced kinase activity (Scott 2002, Verhagen 2009, Demuth 2011, Reiman 2011); Observed in the heterozygous state in individuals with ATM-related cancers (Mandigers 2011, Reiman 2011, Huang 2018, Whitworth 2018); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 26053094, 25572163, 25525159, 21792198, 22146522, 26976419, 30579816, 30549301, 21965147, 21778326, 25957637, 19535770, 25040471, 25980754, 11805335, 16864838, 21354641, 25793145, 26681312, 27060149, 10738255, 15279808, 23566627, 28477129, 28301460, 28126470, 28716242, 25122203, 28843361, 22213089, 29478780, 29909963, 30322717, 30819809, 20301790, 19605768, 31050087, 31920950, 32854451, 32558426, 31980526, 29625052, 33098801, 31447099, 31589614, 23532176, 33594163) -
Pathogenic, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Mar 17, 2020	DNA sequence analysis of the ATM gene demonstrated a sequence change, c.8147T>C, in exon 55 that results in an amino acid change, p.Val2716Ala. This sequence change has been described in the EXAC database with a low population frequency of 0.004% (dbSNP rs587782652).The p.Val2716Ala change affects a highly conserved amino acid residue located in a domain of the ATM protein that is known to be functional. The p.Val2716Ala substitution appears to be deleterious using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). This sequence change has been described in patients with ataxia-telangiectasia in compound heterozygous state (PMID: 21965147, 19535770). Functional in-vitro studies demonstrated that p.Val2716Ala-infected cells had higher radiation-induced chromosome aberrations, when compared to controls (PMID: 11805335). These collective evidences suggest that this sequence change is pathogenic. -
Pathogenic, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Pathogenic, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Pathogenic, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Pathogenic, criteria provided, single submitter	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Oct 07, 2020	PS3, PS4, PM2, PM3, PP3, PP4, PP5 -
Pathogenic, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2024	ATM: PM3:Strong, PP1:Strong, PM2, PP3, PS3:Supporting, PS4:Supporting -

Familial cancer of breast

Pathogenic:8

Likely pathogenic, criteria provided, single submitter	clinical testing	Department of Molecular Diagnostics, Institute of Oncology Ljubljana	Apr 02, 2020	- -
Pathogenic, criteria provided, single submitter	clinical testing	Institute of Human Genetics, University of Leipzig Medical Center	Apr 14, 2022	_x000D_ Criteria applied: PS3, PS4_MOD -
Pathogenic, criteria provided, single submitter	research	Centre for Mendelian Genomics, University Medical Centre Ljubljana	Dec 09, 2022	PS3_MOD, PM3_VSTR , PM5 -
Pathogenic, criteria provided, single submitter	clinical testing	Mendelics	May 04, 2022	- -
Likely pathogenic, criteria provided, single submitter	clinical testing	MGZ Medical Genetics Center	Feb 08, 2022	- -
Likely pathogenic, criteria provided, single submitter	clinical testing	Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine	Jun 05, 2017	This c.8147T>C (p.Val2716Ala) has previously been reported in compound heterozygous patients with ataxia telangiectasia most of them diagnosed in adulthood [PMID 19535770, 16864838, 21965147]. This variant is located in the kinase domain and in vitro data showed reduced kinase activity and lower ATM protein [PMID 11805335]. This variant was observed in 5 individuals at the heterozygous state in the ExAC database (http://exac.broadinstitute.org/variant/11-108205832-T-C). Valine at amino acid position 2716 of the ATM protein is conserved in mammals. While not validated for clinical use, computer-based algorithms SIFT and Polyphen-2 did not yield concordant predictions regarding the pathogenicity of the change. It is thus interpreted as a likely pathogenic variant. However, the estimated cancer risk for this variant has not been determined. -
Pathogenic, criteria provided, single submitter	clinical testing	Baylor Genetics	Mar 28, 2024	- -
Pathogenic, criteria provided, single submitter	clinical testing	Department of Human Genetics, Hannover Medical School	Sep 10, 2024	- -

Hereditary cancer-predisposing syndrome

Pathogenic:4

Likely pathogenic, criteria provided, single submitter	clinical testing	Ambry Genetics	Sep 12, 2023	The p.V2716A variant (also known as c.8147T>C), located in coding exon 54 of the ATM gene, results from a T to C substitution at nucleotide position 8147. The valine at codon 2716 is replaced by alanine, an amino acid with similar properties. This alteration has been reported together with second known pathogenic ATM mutations in multiple individuals with milder, "variant ataxia-telangiectasia" (Verhagen MM et al. Neurology. 2009 Aug;73:430-7; Demuth I et al. Neurogenetics. 2011 Nov;12:273-82; Méneret A, Neurology. 2014 Sep;83:1087-95; Lohmann E et al. J. Neurol. 2015 Jul;262:1724-7; van Os NJH et al. J. Med. Genet., 2019 May;56:308-316; Galatolo D et al. Int J Mol Sci, 2021 Aug;22:). Additionally, this alteration was reported in three unrelated women with ataxia-telangiectasia and breast cancer (Mandigers C et al. Radiother Oncol. 2011 Apr;99:97-8; Reiman A et al. Br. J. Cancer. 2011 Aug;105:586-91). In a multi-gene panel study of patients with bilateral breast cancer, this variant was observed in 1/139 cases (Fanale D et al. Cancers (Basel) 2020 Aug;12(9)). This alteration was also identified in an individual diagnosed with prostate cancer (Wokoorczyk D et al. Int J Cancer, 2020 Nov;147:2793-2800). This alteration has been associated with reduced ATM protein expression, decreased ATM kinase activity, and increased radiosensitivity in studies using A-T lymphoblastoid cell lines (Demuth I et al. Neurogenetics. 2011 Nov;12:273-82; Scott SP et al. Proc. Natl. Acad. Sci. U.S.A. 2002 Jan;99:925-30). Another alteration at the same codon, p.V2716F (c.8146G>T), has been detected in an individual with a clinical diagnosis of ataxia telangiectasia (Hersby DS et al. J Pediatr Hematol Oncol. 2015 Mar;37(2):154-5). 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 majority of available evidence to date, this variant is likely to be pathogenic. -
Likely pathogenic, criteria provided, single submitter	research	Academic Department of Medical Genetics, University of Cambridge	Jan 26, 2018	Application of AMCG guidelines 2015. Used other ClinVar submission evidence where relevant. Loss of heterozygosity in tumours or immunohistochemistry abnormalities considered functional evidence of pathogenicity. -
Pathogenic, criteria provided, single submitter	curation	Sema4, Sema4	Sep 10, 2021	- -
Pathogenic, criteria provided, single submitter	clinical testing	Color Diagnostics, LLC DBA Color Health	Oct 03, 2023	This missense variant replaces valine with alanine at codon 2716 of the kinase domain of ATM protein. Computational prediction tool suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). A functional study has shown that the variant results in the loss of ATM kinase activity and increased radiosensitivity (PMID: 11805335). This variant has been reported in many individuals affected with breast cancer (PMID: 26681312, 26976419, 32854451, 33471991). In a large international case-control study, this variant was reported in 16/60466 breast cancer cases and 6/53461 controls (OR=2.358, 95%CI 0.923 to 6.027, p-value=0.086; PMID: 33471991). This variant has been reported in individuals affected with classic ataxia telangiectasia (PMID: 31050087) and atypical, late-onset ataxia telangiectasia (PMID: 25957637, 16864838, 21354641, 19535770, 21965147, 30819809). This variant has been identified in 9/282750 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Pathogenic. -

Ataxia-telangiectasia syndrome;C0346153:Familial cancer of breast

Pathogenic:2

Likely pathogenic, criteria provided, single submitter	research	HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology	Sep 26, 2022	PS3_Moderate, PS4_Moderate (for AD cancers) or PM3_Strong (for AR ataxia-telangiectasia), PM2_Moderate, PP3_Supporting -
Pathogenic, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	May 31, 2022	- -

Breast and/or ovarian cancer

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

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

Oct 28, 2022

- -

ATM-related disorder

Pathogenic:1

Pathogenic, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 31, 2024

The ATM c.8147T>C variant is predicted to result in the amino acid substitution p.Val2716Ala. This variant has been reported in individuals with ataxia telangiectasia and has been shown to have a reduction or abolished kinase activity (Scott et al. 2002. PubMed ID: 11805335; Demuth et al. 2011. PubMed ID: 21965147). More recently, this variant has been identified in individuals with breast cancer (Table S1, Susswein et al. 2016. PubMed ID: 26681312), colorectal cancer (Table S10, Al Dubayan et al. 2018. PubMed ID: 29478780) and in the tumor of an individual with unspecified cancer type (Whitworth et al. 2018. PubMed ID: 29909963). This variant is reported in 0.0054% of alleles in individuals of European (non-Finnish) descent in gnomAD and is classified in ClinVar as pathogenic or likely pathogenic (https://www.ncbi.nlm.nih.gov/clinvar/variation/142700/). This variant is interpreted as pathogenic. -

Tip-toe gait

Pathogenic:1

Likely pathogenic, no assertion criteria provided

clinical testing

Practice for Gait Abnormalities, David Pomarino, Competency Network Toe Walking c/o Practice Pomarino

Jan 10, 2023

Gait disorder -

Uterine corpus cancer

Pathogenic:1

Pathogenic, no assertion criteria provided

clinical testing

CZECANCA consortium

Feb 21, 2023

- -

Breast carcinoma

Pathogenic:1

Pathogenic, no assertion criteria provided

clinical testing

Medical Genetics Laboratory, Umraniye Training and Research Hospital, University of Health Sciences

Sep 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.92

BayesDel_addAF

Pathogenic

0.34

BayesDel_noAF

Pathogenic

0.40

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.34

T;T

Eigen

Pathogenic

0.72

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.88

D;.

M_CAP

Uncertain

0.29

MetaRNN

Pathogenic

0.96

D;D

MetaSVM

Uncertain

0.72

MutationAssessor

Uncertain

2.1

M;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-3.4

D;D

REVEL

Pathogenic

0.91

Sift

Pathogenic

0.0

D;D

Sift4G

Benign

0.079

T;T

Polyphen

0.99

D;D

Vest4

0.94

MutPred

0.87

Loss of stability (P = 0.0711);Loss of stability (P = 0.0711);

MPC

0.64

ClinPred

0.87

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.71

gMVP

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over