rs2272554

Positions:

• chr16-15756347-A-C
• chr16-15756347-A-G
• chr16-15756347-A-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6 BP7

The NM_002474.3(MYH11):​c.1743T>G​(p.Ala581=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars). Synonymous variant affecting the same amino acid position (i.e. A581A) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYH11 NM_002474.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.675

Genes affected

MYH11 (HGNC:7569): (myosin heavy chain 11) The protein encoded by this gene is a smooth muscle myosin belonging to the myosin heavy chain family. The gene product is a subunit of a hexameric protein that consists of two heavy chain subunits and two pairs of non-identical light chain subunits. It functions as a major contractile protein, converting chemical energy into mechanical energy through the hydrolysis of ATP. A chromosomal rearrangement involving this gene is associated with acute myeloid leukemia of the M4Eo subtype. Mutations in this gene are associated with visceral myopathy, megacystis-microcolon-intestinal hypoperistalsis syndrome 2, and familial thoracic aortic aneurysm 4. [provided by RefSeq, May 2022]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 16-15756347-A-C is Benign according to our data. Variant chr16-15756347-A-C is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-0.675 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH11	NM_002474.3	c.1743T>G	p.Ala581=	synonymous_variant	14/41	ENST00000300036.6
MYH11	NM_001040113.2	c.1764T>G	p.Ala588=	synonymous_variant	15/43	ENST00000452625.7
MYH11	NM_001040114.2	c.1764T>G	p.Ala588=	synonymous_variant	15/42
MYH11	NM_022844.3	c.1743T>G	p.Ala581=	synonymous_variant	14/42

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH11	ENST00000300036.6	c.1743T>G	p.Ala581=	synonymous_variant	14/41	1	NM_002474.3	P3
MYH11	ENST00000452625.7	c.1764T>G	p.Ala588=	synonymous_variant	15/43	1	NM_001040113.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 54

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.098
DANN	Benign	0.59

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: rs2272554; hg19: chr16-15850204;