rs373908250

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_002471.4(MYH6):c.5661+9A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000385 in 1,608,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000037 ( 0 hom. )

Consequence

MYH6
NM_002471.4 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.222

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

hypertrophic cardiomyopathy 14
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Laboratory for Molecular Medicine
Keppen-Lubinsky syndrome
Inheritance: AD Classification: MODERATE Submitted by: Illumina
familial isolated dilated cardiomyopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
atrial septal defect 3
Inheritance: AD Classification: LIMITED Submitted by: G2P
dilated cardiomyopathy
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
hypertrophic cardiomyopathy
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

MYH6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 14-23383216-T-C is Benign according to our data. Variant chr14-23383216-T-C is described in CliVar as Likely_benign. Clinvar id is 414327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23383216-T-C is described in CliVar as Likely_benign. Clinvar id is 414327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23383216-T-C is described in CliVar as Likely_benign. Clinvar id is 414327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23383216-T-C is described in CliVar as Likely_benign. Clinvar id is 414327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23383216-T-C is described in CliVar as Likely_benign. Clinvar id is 414327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23383216-T-C is described in CliVar as Likely_benign. Clinvar id is 414327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23383216-T-C is described in CliVar as Likely_benign. Clinvar id is 414327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23383216-T-C is described in CliVar as Likely_benign. Clinvar id is 414327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23383216-T-C is described in CliVar as Likely_benign. Clinvar id is 414327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23383216-T-C is described in CliVar as Likely_benign. Clinvar id is 414327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23383216-T-C is described in CliVar as Likely_benign. Clinvar id is 414327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23383216-T-C is described in CliVar as Likely_benign. Clinvar id is 414327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23383216-T-C is described in CliVar as Likely_benign. Clinvar id is 414327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23383216-T-C is described in CliVar as Likely_benign. Clinvar id is 414327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23383216-T-C is described in CliVar as Likely_benign. Clinvar id is 414327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23383216-T-C is described in CliVar as Likely_benign. Clinvar id is 414327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23383216-T-C is described in CliVar as Likely_benign. Clinvar id is 414327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23383216-T-C is described in CliVar as Likely_benign. Clinvar id is 414327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23383216-T-C is described in CliVar as Likely_benign. Clinvar id is 414327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23383216-T-C is described in CliVar as Likely_benign. Clinvar id is 414327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23383216-T-C is described in CliVar as Likely_benign. Clinvar id is 414327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23383216-T-C is described in CliVar as Likely_benign. Clinvar id is 414327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23383216-T-C is described in CliVar as Likely_benign. Clinvar id is 414327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23383216-T-C is described in CliVar as Likely_benign. Clinvar id is 414327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23383216-T-C is described in CliVar as Likely_benign. Clinvar id is 414327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23383216-T-C is described in CliVar as Likely_benign. Clinvar id is 414327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23383216-T-C is described in CliVar as Likely_benign. Clinvar id is 414327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23383216-T-C is described in CliVar as Likely_benign. Clinvar id is 414327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23383216-T-C is described in CliVar as Likely_benign. Clinvar id is 414327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23383216-T-C is described in CliVar as Likely_benign. Clinvar id is 414327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23383216-T-C is described in CliVar as Likely_benign. Clinvar id is 414327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23383216-T-C is described in CliVar as Likely_benign. Clinvar id is 414327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23383216-T-C is described in CliVar as Likely_benign. Clinvar id is 414327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23383216-T-C is described in CliVar as Likely_benign. Clinvar id is 414327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23383216-T-C is described in CliVar as Likely_benign. Clinvar id is 414327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23383216-T-C is described in CliVar as Likely_benign. Clinvar id is 414327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23383216-T-C is described in CliVar as Likely_benign. Clinvar id is 414327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23383216-T-C is described in CliVar as Likely_benign. Clinvar id is 414327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23383216-T-C is described in CliVar as Likely_benign. Clinvar id is 414327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23383216-T-C is described in CliVar as Likely_benign. Clinvar id is 414327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23383216-T-C is described in CliVar as Likely_benign. Clinvar id is 414327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23383216-T-C is described in CliVar as Likely_benign. Clinvar id is 414327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23383216-T-C is described in CliVar as Likely_benign. Clinvar id is 414327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH6	NM_002471.4 link	c.5661+9A>G		intron_variant	Intron 37 of 38	ENST00000405093.9	NP_002462.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH6	ENST00000405093.9 link	c.5661+9A>G		intron_variant	Intron 37 of 38	5	NM_002471.4	ENSP00000386041.3		P13533
MYH6	ENST00000651452.1 link	n.888+9A>G		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.0000527

AC:

AN:

151710

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000198

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:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000836

AC:

AN:

251342

AF XY:

0.0000883

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000434

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000371

AC:

AN:

1456850

Hom.:

Cov.:

AF XY:

0.0000345

AC XY:

AN XY:

724904

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33328

American (AMR)

AF:

0.000537

AC:

AN:

44652

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26068

East Asian (EAS)

AF:

0.00

AC:

AN:

39538

South Asian (SAS)

AF:

0.00

AC:

AN:

86150

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53238

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4856

European-Non Finnish (NFE)

AF:

0.0000253

AC:

AN:

1108878

Other (OTH)

AF:

0.0000333

AC:

AN:

60142

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000527

AC:

AN:

151826

Hom.:

Cov.:

AF XY:

0.0000674

AC XY:

AN XY:

74230

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41392

American (AMR)

AF:

0.000198

AC:

AN:

15156

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5154

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10546

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000736

AC:

AN:

67976

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000900

Hom.:

Bravo

AF:

0.000113

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hypertrophic cardiomyopathy 14

Benign:1

Dec 02, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

Jul 23, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

MYH6-related disorder

Benign:1

Jun 14, 2023

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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

8.1

(source)

DANN

Benign

0.65

PhyloP100

0.22

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over