NM_017534.6:c.1975-47A>T

Variant names:

• chr17-10535412-T-A
• rs3744567
• NM_017534.6:c.1975-47A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017534.6(MYH2):​c.1975-47A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000752 in 1,330,270 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: MYH2 NM_017534.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.136
• Publications: 0 publications found

Genes affected

MYH2 (HGNC:7572): (myosin heavy chain 2) Myosins are actin-based motor proteins that function in the generation of mechanical force in eukaryotic cells. Muscle myosins are heterohexamers composed of 2 myosin heavy chains and 2 pairs of nonidentical myosin light chains. This gene encodes a member of the class II or conventional myosin heavy chains, and functions in skeletal muscle contraction. This gene is found in a cluster of myosin heavy chain genes on chromosome 17. A mutation in this gene results in inclusion body myopathy-3. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Sep 2009]

MYHAS (HGNC:50609): (myosin heavy chain gene cluster antisense RNA) Predicted to enable primary miRNA binding activity. Predicted to be involved in response to muscle activity and skeletal muscle fiber development. Predicted to act upstream of or within with a positive effect on gene expression. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH2	NM_017534.6	c.1975-47A>T		intron_variant	Intron 17 of 39	ENST00000245503.10	NP_060004.3
MYH2	NM_001100112.2	c.1975-47A>T		intron_variant	Intron 17 of 39		NP_001093582.1
MYHAS	NR_125367.1	n.168-32125T>A		intron_variant	Intron 2 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH2	ENST00000245503.10	c.1975-47A>T		intron_variant	Intron 17 of 39	1	NM_017534.6	ENSP00000245503.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.52e-7 AC: 1 AN: 1330270 Hom.: 0 Cov.: 21 AF XY: 0.00000150 AC XY: 1 AN XY: 668370

African (AFR) AF: 0.00 AC: 0 AN: 30708

American (AMR) AF: 0.00 AC: 0 AN: 43784

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25286

East Asian (EAS) AF: 0.00 AC: 0 AN: 38908

South Asian (SAS) AF: 0.00 AC: 0 AN: 83146

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53074

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5484

European-Non Finnish (NFE) AF: 0.00000101 AC: 1 AN: 993904

Other (OTH) AF: 0.00 AC: 0 AN: 55976

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.2
DANN	Benign	0.62
PhyloP100		-0.14

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: rs3744567; hg19: chr17-10438729;