2-190056335-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005259.3(MSTN):c.*923T>C variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.000158 in 152,166 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MSTN
NM_005259.3 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.80

Variant links:

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]

MSTN links:

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]

C2orf88 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
MSTN	NM_005259.3 linkuse as main transcript	c.*923T>C	3_prime_UTR_variant	3/3	ENST00000260950.5
C2orf88	XM_047446008.1 linkuse as main transcript	c.-517-23619A>G	intron_variant
C2orf88	XM_047446009.1 linkuse as main transcript	c.-517-23619A>G	intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris
MSTN	ENST00000260950.5 linkuse as main transcript	c.*923T>C	3_prime_UTR_variant	3/3	1	NM_005259.3	P1
C2orf88	ENST00000478197.1 linkuse as main transcript	n.220-22888A>G	intron_variant, non_coding_transcript_variant		4
C2orf88	ENST00000495546.1 linkuse as main transcript	n.202-23619A>G	intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000478

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

432

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

260

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000158

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000208

Hom.:

Bravo

AF:

0.000215

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Myostatin-related muscle hypertrophy

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

Cadd

Benign

Dann

Benign

0.78

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over