rs560271582

Positions:

• chr14-23400245-CA-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_002471.4(MYH6):​c.1581+10del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000479 in 152,282 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00048 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000071 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MYH6 NM_002471.4 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.322

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 -12 ACMG points.

• BP6: Variant 14-23400245-CA-C is Benign according to our data. Variant chr14-23400245-CA-C is described in ClinVar as [Likely_benign]. Clinvar id is 422646.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 73 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH6	NM_002471.4	c.1581+10del		intron_variant		ENST00000405093.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH6	ENST00000405093.9	c.1581+10del		intron_variant		5	NM_002471.4	P1
MYH6	ENST00000557461.2	n.1658del		non_coding_transcript_exon_variant	14/14	5

Frequencies

GnomAD3 genomes AF: 0.000480 AC: 73 AN: 152164 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00171

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000179 AC: 45 AN: 251448 Hom.: 0 AF XY: 0.000125 AC XY: 17 AN XY: 135916

Gnomad AFR exome AF: 0.00197

Gnomad AMR exome AF: 0.000260

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000163

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000711 AC: 104 AN: 1461882 Hom.: 0 Cov.: 31 AF XY: 0.0000550 AC XY: 40 AN XY: 727240

Gnomad4 AFR exome AF: 0.00206

Gnomad4 AMR exome AF: 0.000291

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.000298

GnomAD4 genome AF: 0.000479 AC: 73 AN: 152282 Hom.: 0 Cov.: 32 AF XY: 0.000443 AC XY: 33 AN XY: 74442

Gnomad4 AFR AF: 0.00171

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000285 Hom.: 0

Bravo AF: 0.000525

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 03, 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. -

Hypertrophic cardiomyopathy 14 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 06, 2023

- -

MYH6-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 17, 2019

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

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs560271582; hg19: chr14-23869454;