chr14-23407007-G-A

Variant names:

• chr14-23407007-G-A
• rs7147244
• NM_002471.4:c.201+16C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002471.4(MYH6):​c.201+16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0381 in 1,612,258 control chromosomes in the GnomAD database, including 1,700 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.058 (431 hom., cov: 32)
  • Exomes 𝑓: 0.036 (1269 hom.)
• Consequence: MYH6 NM_002471.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -2.21
• Publications: 5 publications found

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BP6: Variant 14-23407007-G-A is Benign according to our data. Variant chr14-23407007-G-A is described in ClinVar as Benign. ClinVar VariationId is 258708.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002471.4. 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
	MYH6	NM_002471.4	MANE Select	c.201+16C>T		intron	N/A	NP_002462.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH6	ENST00000405093.9	TSL:5 MANE Select	c.201+16C>T		intron	N/A	ENSP00000386041.3
	MYH6	ENST00000557461.2	TSL:5	n.268+16C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0577 AC: 8768 AN: 151924 Hom.: 428 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0318

Gnomad ASJ AF: 0.0254

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00688

Gnomad FIN AF: 0.00661

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0354

Gnomad OTH AF: 0.0483

GnomAD2 exomes AF: 0.0293 AC: 7361 AN: 251098 AF XY: 0.0273

Gnomad AFR exome AF: 0.134

Gnomad AMR exome AF: 0.0196

Gnomad ASJ exome AF: 0.0248

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00701

Gnomad NFE exome AF: 0.0331

Gnomad OTH exome AF: 0.0269

GnomAD4 exome AF: 0.0360 AC: 52561 AN: 1460216 Hom.: 1269 Cov.: 31 AF XY: 0.0347 AC XY: 25228 AN XY: 726556

African (AFR) AF: 0.139 AC: 4645 AN: 33446

American (AMR) AF: 0.0224 AC: 1000 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0262 AC: 686 AN: 26134

East Asian (EAS) AF: 0.000227 AC: 9 AN: 39692

South Asian (SAS) AF: 0.00591 AC: 509 AN: 86190

European-Finnish (FIN) AF: 0.00794 AC: 423 AN: 53242

Middle Eastern (MID) AF: 0.0222 AC: 128 AN: 5766

European-Non Finnish (NFE) AF: 0.0388 AC: 43127 AN: 1110668

Other (OTH) AF: 0.0337 AC: 2034 AN: 60358

GnomAD4 genome AF: 0.0578 AC: 8790 AN: 152042 Hom.: 431 Cov.: 32 AF XY: 0.0554 AC XY: 4115 AN XY: 74326

African (AFR) AF: 0.135 AC: 5583 AN: 41454

American (AMR) AF: 0.0318 AC: 486 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0254 AC: 88 AN: 3466

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5182

South Asian (SAS) AF: 0.00668 AC: 32 AN: 4794

European-Finnish (FIN) AF: 0.00661 AC: 70 AN: 10592

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0354 AC: 2404 AN: 67954

Other (OTH) AF: 0.0478 AC: 101 AN: 2114

Alfa AF: 0.0419 Hom.: 243

Bravo AF: 0.0640

Asia WGS AF: 0.0210 AC: 74 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:5

Sep 29, 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.

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

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

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.041
DANN	Benign	0.50
PhyloP100		-2.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7147244; hg19: chr14-23876216;