rs8022522

Variant names:

• chr14-23388142-G-A
• rs8022522
• NM_002471.4:c.4359+13C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-23388142-G-A
• chr14-23388142-G-C
• chr14-23388142-G-T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_002471.4(MYH6):​c.4359+13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 1,611,892 control chromosomes in the GnomAD database, including 119,072 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.45 (17833 hom., cov: 32)
  • Exomes 𝑓: 0.36 (101239 hom.)
• Consequence: MYH6 NM_002471.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -2.48
• Publications: 9 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 -16 ACMG points.

• BP6: Variant 14-23388142-G-A is Benign according to our data. Variant chr14-23388142-G-A is described in ClinVar as Benign. ClinVar VariationId is 44510.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.724 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.4359+13C>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.4359+13C>T		intron	N/A	ENSP00000386041.3

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68190 AN: 151882 Hom.: 17787 Cov.: 32

Gnomad AFR AF: 0.731

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.450

GnomAD2 exomes AF: 0.344 AC: 86318 AN: 250876 AF XY: 0.343

Gnomad AFR exome AF: 0.737

Gnomad AMR exome AF: 0.232

Gnomad ASJ exome AF: 0.417

Gnomad EAS exome AF: 0.164

Gnomad FIN exome AF: 0.265

Gnomad NFE exome AF: 0.360

Gnomad OTH exome AF: 0.361

GnomAD4 exome AF: 0.364 AC: 531374 AN: 1459892 Hom.: 101239 Cov.: 64 AF XY: 0.362 AC XY: 262719 AN XY: 726240

African (AFR) AF: 0.736 AC: 24608 AN: 33414

American (AMR) AF: 0.246 AC: 10994 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 10753 AN: 26134

East Asian (EAS) AF: 0.147 AC: 5842 AN: 39698

South Asian (SAS) AF: 0.340 AC: 29340 AN: 86172

European-Finnish (FIN) AF: 0.268 AC: 14294 AN: 53334

Middle Eastern (MID) AF: 0.398 AC: 1669 AN: 4190

European-Non Finnish (NFE) AF: 0.370 AC: 411391 AN: 1111994

Other (OTH) AF: 0.373 AC: 22483 AN: 60232

GnomAD4 genome AF: 0.449 AC: 68295 AN: 152000 Hom.: 17833 Cov.: 32 AF XY: 0.441 AC XY: 32754 AN XY: 74294

African (AFR) AF: 0.731 AC: 30317 AN: 41454

American (AMR) AF: 0.343 AC: 5234 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 1464 AN: 3472

East Asian (EAS) AF: 0.162 AC: 831 AN: 5140

South Asian (SAS) AF: 0.332 AC: 1596 AN: 4814

European-Finnish (FIN) AF: 0.271 AC: 2865 AN: 10568

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.361 AC: 24557 AN: 67960

Other (OTH) AF: 0.457 AC: 963 AN: 2108

Alfa AF: 0.395 Hom.: 19651

Bravo AF: 0.466

Asia WGS AF: 0.317 AC: 1101 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not specified (6)
-	-	2	not provided (2)
-	-	1	Hypertrophic cardiomyopathy 14 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.7
DANN	Benign	0.70
PhyloP100		-2.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.35		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.35		Position offset: 2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs8022522; hg19: chr14-23857351; COSMIC: COSV62448783; COSMIC: COSV62448783;