14-23389062-AGGG-AG

Variant names:

• chr14-23389062-AGG-A
• rs193922652
• NM_002471.4:c.3979-9_3979-8delCC

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_002471.4(MYH6):​c.3979-9_3979-8delCC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (763 hom., cov: 0)
  • Exomes 𝑓: 0.14 (11301 hom.)
  • Failed GnomAD Quality Control
• Consequence: MYH6 NM_002471.4 splice_region, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.275

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 14-23389062-AGG-A is Benign according to our data. Variant chr14-23389062-AGG-A is described in ClinVar as [Benign]. Clinvar id is 220788.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23389062-AGG-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH6	NM_002471.4	c.3979-9_3979-8delCC		splice_region_variant, intron_variant	Intron 28 of 38	ENST00000405093.9	NP_002462.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH6	ENST00000405093.9	c.3979-9_3979-8delCC		splice_region_variant, intron_variant	Intron 28 of 38	5	NM_002471.4	ENSP00000386041.3

Frequencies

GnomAD3 genomes AF: 0.129 AC: 14951 AN: 115620 Hom.: 761 Cov.: 0

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.0912

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.000657

Gnomad SAS AF: 0.0461

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.0969

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.121

GnomAD3 exomes AF: 0.122 AC: 17018 AN: 139674 Hom.: 903 AF XY: 0.120 AC XY: 9184 AN XY: 76278

Gnomad AFR exome AF: 0.115

Gnomad AMR exome AF: 0.0826

Gnomad ASJ exome AF: 0.199

Gnomad EAS exome AF: 0.000548

Gnomad SAS exome AF: 0.0553

Gnomad FIN exome AF: 0.132

Gnomad NFE exome AF: 0.159

Gnomad OTH exome AF: 0.130

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.141 AC: 149380 AN: 1057912 Hom.: 11301 AF XY: 0.137 AC XY: 72412 AN XY: 527248

Gnomad4 AFR exome AF: 0.112

Gnomad4 AMR exome AF: 0.0667

Gnomad4 ASJ exome AF: 0.180

Gnomad4 EAS exome AF: 0.000180

Gnomad4 SAS exome AF: 0.0497

Gnomad4 FIN exome AF: 0.107

Gnomad4 NFE exome AF: 0.159

Gnomad4 OTH exome AF: 0.133

GnomAD4 genome AF: 0.129 AC: 14958 AN: 115736 Hom.: 763 Cov.: 0 AF XY: 0.125 AC XY: 7118 AN XY: 56878

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.0912

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.000659

Gnomad4 SAS AF: 0.0460

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.119

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:5

-

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

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Nov 07, 2017

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. -

-

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

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Aug 16, 2019

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

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

- -

Cardiomyopathy Benign:1

Mar 08, 2018

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

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs193922652; hg19: chr14-23858271;