2-147903474-G-T

Variant names:

• chr2-147903474-G-T
• rs7581537
• NM_001616.5:c.528+3576G>T

Variant summary

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

The NM_001616.5(ACVR2A):​c.528+3576G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.897 in 151,770 control chromosomes in the GnomAD database, including 62,618 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 0.90 (62618 hom., cov: 29)
• Consequence: ACVR2A NM_001616.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.118
• Publications: 3 publications found

Genes affected

ACVR2A (HGNC:173): (activin A receptor type 2A) This gene encodes a receptor that mediates the functions of activins, which are members of the transforming growth factor-beta (TGF-beta) superfamily involved in diverse biological processes. The encoded protein is a transmembrane serine-threonine kinase receptor which mediates signaling by forming heterodimeric complexes with various combinations of type I and type II receptors and ligands in a cell-specific manner. The encoded type II receptor is primarily involved in ligand-binding and includes an extracellular ligand-binding domain, a transmembrane domain and a cytoplasmic serine-threonine kinase domain. This gene may be associated with susceptibility to preeclampsia, a pregnancy-related disease which can result in maternal and fetal morbidity and mortality. Alternative splicing results in multiple transcript variants of this gene. [provided by RefSeq, Jun 2013]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.982 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACVR2A	NM_001616.5	c.528+3576G>T		intron_variant	Intron 4 of 10	ENST00000241416.12	NP_001607.1
ACVR2A	NM_001278579.2	c.528+3576G>T		intron_variant	Intron 5 of 11		NP_001265508.1
ACVR2A	NM_001278580.2	c.204+3576G>T		intron_variant	Intron 4 of 10		NP_001265509.1
ACVR2A	XM_047446292.1	c.204+3576G>T		intron_variant	Intron 4 of 10		XP_047302248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACVR2A	ENST00000241416.12	c.528+3576G>T		intron_variant	Intron 4 of 10	1	NM_001616.5	ENSP00000241416.7
ACVR2A	ENST00000404590.1	c.528+3576G>T		intron_variant	Intron 5 of 11	1		ENSP00000384338.1
ACVR2A	ENST00000535787.5	c.204+3576G>T		intron_variant	Intron 4 of 10	2		ENSP00000439988.1

Frequencies

GnomAD3 genomes AF: 0.897 AC: 136028 AN: 151650 Hom.: 62579 Cov.: 29

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.954

Gnomad AMR AF: 0.951

Gnomad ASJ AF: 0.992

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.998

Gnomad FIN AF: 0.999

Gnomad MID AF: 0.956

Gnomad NFE AF: 0.989

Gnomad OTH AF: 0.913

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

GnomAD4 genome AF: 0.897 AC: 136126 AN: 151770 Hom.: 62618 Cov.: 29 AF XY: 0.901 AC XY: 66835 AN XY: 74172

African (AFR) AF: 0.665 AC: 27524 AN: 41366

American (AMR) AF: 0.951 AC: 14457 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.992 AC: 3436 AN: 3464

East Asian (EAS) AF: 1.00 AC: 5164 AN: 5164

South Asian (SAS) AF: 0.998 AC: 4818 AN: 4826

European-Finnish (FIN) AF: 0.999 AC: 10593 AN: 10608

Middle Eastern (MID) AF: 0.963 AC: 283 AN: 294

European-Non Finnish (NFE) AF: 0.989 AC: 67053 AN: 67826

Other (OTH) AF: 0.914 AC: 1928 AN: 2110

Alfa AF: 0.949 Hom.: 14963

Bravo AF: 0.882

Asia WGS AF: 0.978 AC: 3402 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.2
DANN	Benign	0.31
PhyloP100		0.12
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: rs7581537; hg19: chr2-148661043;