14-23384532-C-T

Position:

chr14-23384532-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_002471.4(MYH6):c.5475G>A(p.Glu1825Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00248 in 1,613,426 control chromosomes in the GnomAD database, including 67 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0031 ( 7 hom., cov: 33)

Exomes 𝑓: 0.0024 ( 60 hom. )

Consequence

MYH6
NM_002471.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.184

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 -16 ACMG points.

BP6

Variant 14-23384532-C-T is Benign according to our data. Variant chr14-23384532-C-T is described in ClinVar as [Benign]. Clinvar id is 44537.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23384532-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00306 (466/152340) while in subpopulation EAS AF= 0.0469 (243/5186). AF 95% confidence interval is 0.042. There are 7 homozygotes in gnomad4. There are 243 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 466 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH6	NM_002471.4 linkuse as main transcript	c.5475G>A	p.Glu1825Glu	synonymous_variant	36/39	ENST00000405093.9	NP_002462.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH6	ENST00000405093.9 linkuse as main transcript	c.5475G>A	p.Glu1825Glu	synonymous_variant	36/39	5	NM_002471.4	ENSP00000386041.3		P13533

Frequencies

GnomAD3 genomes

AF:

0.00303

AC:

462

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0103

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.0465

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00789

AC:

1983

AN:

251362

Hom.:

AF XY:

0.00628

AC XY:

853

AN XY:

135882

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.0318

Gnomad ASJ exome

AF:

0.00347

Gnomad EAS exome

AF:

0.0381

Gnomad SAS exome

AF:

0.00287

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000149

Gnomad OTH exome

AF:

0.00587

GnomAD4 exome

AF:

0.00242

AC:

3536

AN:

1461086

Hom.:

Cov.:

AF XY:

0.00224

AC XY:

1628

AN XY:

726844

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.0299

Gnomad4 ASJ exome

AF:

0.00367

Gnomad4 EAS exome

AF:

0.0386

Gnomad4 SAS exome

AF:

0.00244

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.000103

Gnomad4 OTH exome

AF:

0.00375

GnomAD4 genome

AF:

0.00306

AC:

466

AN:

152340

Hom.:

Cov.:

AF XY:

0.00326

AC XY:

243

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.000722

Gnomad4 AMR

AF:

0.0104

Gnomad4 ASJ

AF:

0.00230

Gnomad4 EAS

AF:

0.0469

Gnomad4 SAS

AF:

0.00332

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000499

Hom.:

Bravo

AF:

0.00464

Asia WGS

AF:

0.0180

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 23, 2016	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. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Nov 30, 2011	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	May 28, 2020	- -

Hypertrophic cardiomyopathy 14

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 28, 2024

- -

Dilated cardiomyopathy 1EE;C2750467:Hypertrophic cardiomyopathy 14;C3279790:Atrial septal defect 3;C3279791:Sick sinus syndrome 3, susceptibility to;C3495498:Hypertrophic cardiomyopathy 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Jul 20, 2021

- -

Cardiomyopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

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

Oct 23, 2015

- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 20, 2016

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

-0.43

CADD

Benign

DANN

Benign

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.32

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.32

Position offset: -1

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