rs76202964

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002471.4(MYH6):c.2151C>T(p.Tyr717Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0153 in 1,613,146 control chromosomes in the GnomAD database, including 491 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 53 hom., cov: 33)

Exomes 𝑓: 0.015 ( 438 hom. )

Consequence

MYH6
NM_002471.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.0480

Variant links:

Genes affected

MYH6 (HGNC:7576): (myosin heavy chain 6) Cardiac muscle myosin is a hexamer consisting of two heavy chain subunits, two light chain subunits, and two regulatory subunits. This gene encodes the alpha heavy chain subunit of cardiac myosin. The gene is located approximately 4kb downstream of the gene encoding the beta heavy chain subunit of cardiac myosin. Mutations in this gene cause familial hypertrophic cardiomyopathy and atrial septal defect 3. [provided by RefSeq, Feb 2017]

MYH6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 14-23396980-G-A is Benign according to our data. Variant chr14-23396980-G-A is described in ClinVar as [Benign]. Clinvar id is 44461.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23396980-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.048 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0752 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH6	NM_002471.4 link	c.2151C>T	p.Tyr717Tyr	synonymous_variant	Exon 18 of 39	ENST00000405093.9	NP_002462.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH6	ENST00000405093.9 link	c.2151C>T	p.Tyr717Tyr	synonymous_variant	Exon 18 of 39	5	NM_002471.4	ENSP00000386041.3		P13533

Frequencies

GnomAD3 genomes

AF:

0.0161

AC:

2450

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00808

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0262

Gnomad ASJ

AF:

0.0495

Gnomad EAS

AF:

0.0816

Gnomad SAS

AF:

0.0366

Gnomad FIN

AF:

0.00612

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0116

Gnomad OTH

AF:

0.0301

GnomAD3 exomes

AF:

0.0242

AC:

6093

AN:

251410

Hom.:

165

AF XY:

0.0243

AC XY:

3308

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.00886

Gnomad AMR exome

AF:

0.0363

Gnomad ASJ exome

AF:

0.0397

Gnomad EAS exome

AF:

0.0841

Gnomad SAS exome

AF:

0.0331

Gnomad FIN exome

AF:

0.00651

Gnomad NFE exome

AF:

0.0125

Gnomad OTH exome

AF:

0.0280

GnomAD4 exome

AF:

0.0152

AC:

22166

AN:

1460830

Hom.:

438

Cov.:

AF XY:

0.0159

AC XY:

11553

AN XY:

726738

show subpopulations

Gnomad4 AFR exome

AF:

0.00921

Gnomad4 AMR exome

AF:

0.0352

Gnomad4 ASJ exome

AF:

0.0420

Gnomad4 EAS exome

AF:

0.0859

Gnomad4 SAS exome

AF:

0.0320

Gnomad4 FIN exome

AF:

0.00567

Gnomad4 NFE exome

AF:

0.0100

Gnomad4 OTH exome

AF:

0.0211

GnomAD4 genome

AF:

0.0163

AC:

2478

AN:

152316

Hom.:

Cov.:

AF XY:

0.0172

AC XY:

1281

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00839

Gnomad4 AMR

AF:

0.0263

Gnomad4 ASJ

AF:

0.0495

Gnomad4 EAS

AF:

0.0816

Gnomad4 SAS

AF:

0.0369

Gnomad4 FIN

AF:

0.00612

Gnomad4 NFE

AF:

0.0116

Gnomad4 OTH

AF:

0.0384

Alfa

AF:

0.0161

Hom.:

Bravo

AF:

0.0187

Asia WGS

AF:

0.0710

AC:

246

AN:

3478

EpiCase

AF:

0.0172

EpiControl

AF:

0.0168

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 04, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

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

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

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

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Dec 01, 2011

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hypertrophic cardiomyopathy 14

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Cardiovascular phenotype

Benign:1

Aug 21, 2015

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

0.087

DANN

Benign

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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