2-190056112-AT-A

Position:

• chr2-190056112-AT-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_005259.3(MSTN):​c.*1145del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0113 in 152,206 control chromosomes in the GnomAD database, including 27 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (27 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MSTN NM_005259.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.662

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 Benign. Variant got -10 ACMG points.

• BP6: Variant 2-190056112-AT-A is Benign according to our data. Variant chr2-190056112-AT-A is described in ClinVar as [Likely_benign]. Clinvar id is 333220.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0113 (1721/152206) while in subpopulation AFR AF= 0.0389 (1615/41534). AF 95% confidence interval is 0.0373. There are 27 homozygotes in gnomad4. There are 821 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 27 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSTN	NM_005259.3	c.*1145del		3_prime_UTR_variant	3/3	ENST00000260950.5	NP_005250.1
C2orf88	XM_047446008.1	c.-517-23841del		intron_variant			XP_047301964.1
C2orf88	XM_047446009.1	c.-517-23841del		intron_variant			XP_047301965.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSTN	ENST00000260950.5	c.*1145del		3_prime_UTR_variant	3/3	1	NM_005259.3	ENSP00000260950	P1
C2orf88	ENST00000478197.1	n.220-23110del		intron_variant, non_coding_transcript_variant		4
C2orf88	ENST00000495546.1	n.202-23841del		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0112 AC: 1710 AN: 152088 Hom.: 26 Cov.: 32

Gnomad AFR AF: 0.0387

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00498

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00957

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 432 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 260

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0113 AC: 1721 AN: 152206 Hom.: 27 Cov.: 32 AF XY: 0.0110 AC XY: 821 AN XY: 74432

Gnomad4 AFR AF: 0.0389

Gnomad4 AMR AF: 0.00497

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00947

Alfa AF: 0.00166 Hom.: 1

Bravo AF: 0.0130

Asia WGS AF: 0.00261 AC: 9 AN: 3464

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Myostatin-related muscle hypertrophy Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs199602321; hg19: chr2-190920838;