2-190058686-A-G

Variant names:

• chr2-190058686-A-G
• rs7570532
• NM_005259.3:c.748-1048T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005259.3(MSTN):​c.748-1048T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 151,868 control chromosomes in the GnomAD database, including 11,240 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 0.33 (11240 hom., cov: 32)
• Consequence: MSTN NM_005259.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.216
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSTN	NM_005259.3	c.748-1048T>C		intron_variant	Intron 2 of 2	ENST00000260950.5	NP_005250.1
AKAP19	XM_047446008.1	c.-517-21268A>G		intron_variant	Intron 2 of 6		XP_047301964.1
AKAP19	XM_047446009.1	c.-517-21268A>G		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.748-1048T>C		intron_variant	Intron 2 of 2	1	NM_005259.3	ENSP00000260950.3
C2orf88	ENST00000478197.1	n.220-20537A>G		intron_variant	Intron 1 of 1	4
C2orf88	ENST00000495546.1	n.202-21268A>G		intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes AF: 0.329 AC: 49859 AN: 151750 Hom.: 11200 Cov.: 32

Gnomad AFR AF: 0.644

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.321

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

GnomAD4 genome AF: 0.329 AC: 49953 AN: 151868 Hom.: 11240 Cov.: 32 AF XY: 0.321 AC XY: 23855 AN XY: 74258

African (AFR) AF: 0.644 AC: 26690 AN: 41416

American (AMR) AF: 0.257 AC: 3917 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 1005 AN: 3466

East Asian (EAS) AF: 0.254 AC: 1314 AN: 5166

South Asian (SAS) AF: 0.169 AC: 816 AN: 4822

European-Finnish (FIN) AF: 0.136 AC: 1438 AN: 10610

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.205 AC: 13897 AN: 67854

Other (OTH) AF: 0.322 AC: 679 AN: 2106

Alfa AF: 0.265 Hom.: 892

Bravo AF: 0.355

Asia WGS AF: 0.247 AC: 858 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.2
DANN	Benign	0.65
PhyloP100		-0.22
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7570532; hg19: chr2-190923412;