rs35781413

Variant names:

• chr2-190060319-C-A
• NM_005259.3:c.490G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-190060319-C-A
• chr2-190060319-C-G
• chr2-190060319-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005259.3(MSTN):​c.490G>T​(p.Glu164*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MSTN NM_005259.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22

Genes affected

MSTN (HGNC:4223): (myostatin) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. This protein negatively regulates skeletal muscle cell proliferation and differentiation. Mutations in this gene are associated with increased skeletal muscle mass in humans and other mammals. [provided by RefSeq, Jul 2016]

C2orf88 (HGNC:28191): (chromosome 2 open reading frame 88) Predicted to enable protein kinase A regulatory subunit binding activity. Predicted to be located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSTN	NM_005259.3	c.490G>T	p.Glu164*	stop_gained	Exon 2 of 3	ENST00000260950.5	NP_005250.1
C2orf88	XM_047446008.1	c.-517-19635C>A		intron_variant	Intron 2 of 6		XP_047301964.1
C2orf88	XM_047446009.1	c.-517-19635C>A		intron_variant	Intron 1 of 5		XP_047301965.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSTN	ENST00000260950.5	c.490G>T	p.Glu164*	stop_gained	Exon 2 of 3	1	NM_005259.3	ENSP00000260950.3
C2orf88	ENST00000478197.1	n.220-18904C>A		intron_variant	Intron 1 of 1	4
C2orf88	ENST00000495546.1	n.202-19635C>A		intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.57	D
BayesDel_noAF	Pathogenic	0.59
CADD	Pathogenic	35
DANN	Uncertain	1.0
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.81	D
Vest4		0.94
GERP RS		1.6

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-190925045;