chr17-10548996-A-G

Position:

• chr17-10548996-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017534.6(MYH2):​c.-21+379T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 152,096 control chromosomes in the GnomAD database, including 14,161 homozygotes. 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: 𝑓 0.42 (14161 hom., cov: 33)
• Consequence: MYH2 NM_017534.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH2	NM_017534.6	c.-21+379T>C		intron_variant		ENST00000245503.10	NP_060004.3
MYHAS	NR_125367.1	n.168-18541A>G		intron_variant, non_coding_transcript_variant
MYH2	NM_001100112.2	c.-21+379T>C		intron_variant			NP_001093582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH2	ENST00000245503.10	c.-21+379T>C		intron_variant		1	NM_017534.6	ENSP00000245503	P1

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63410 AN: 151978 Hom.: 14144 Cov.: 33

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.491

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.851

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.403

Gnomad OTH AF: 0.413

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.417 AC: 63472 AN: 152096 Hom.: 14161 Cov.: 33 AF XY: 0.429 AC XY: 31910 AN XY: 74342

Gnomad4 AFR AF: 0.323

Gnomad4 AMR AF: 0.492

Gnomad4 ASJ AF: 0.448

Gnomad4 EAS AF: 0.851

Gnomad4 SAS AF: 0.618

Gnomad4 FIN AF: 0.452

Gnomad4 NFE AF: 0.403

Gnomad4 OTH AF: 0.413

Alfa AF: 0.412 Hom.: 12622

Bravo AF: 0.415

Asia WGS AF: 0.669 AC: 2324 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	11
DANN	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs3760431; hg19: chr17-10452313; COSMIC: COSV55434408; COSMIC: COSV55434408;