2-147905999-G-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001616.5(ACVR2A):c.528+6101G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 151,936 control chromosomes in the GnomAD database, including 5,912 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 0.26 (5912 hom., cov: 31)
• Consequence: ACVR2A NM_001616.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

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

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACVR2A	NM_001616.5	c.528+6101G>T		intron_variant		ENST00000241416.12
ACVR2A	NM_001278579.2	c.528+6101G>T		intron_variant
ACVR2A	NM_001278580.2	c.204+6101G>T		intron_variant
ACVR2A	XM_047446292.1	c.204+6101G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACVR2A	ENST00000241416.12	c.528+6101G>T		intron_variant		1	NM_001616.5	P1
ACVR2A	ENST00000404590.1	c.528+6101G>T		intron_variant		1		P1
ACVR2A	ENST00000535787.5	c.204+6101G>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39278 AN: 151816 Hom.: 5916 Cov.: 31

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.382

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.293

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

GnomAD4 genome AF: 0.259 AC: 39291 AN: 151936 Hom.: 5912 Cov.: 31 AF XY: 0.261 AC XY: 19410 AN XY: 74246

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.308

Gnomad4 ASJ AF: 0.314

Gnomad4 EAS AF: 0.460

Gnomad4 SAS AF: 0.290

Gnomad4 FIN AF: 0.334

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.293

Alfa AF: 0.288 Hom.: 4024

Bravo AF: 0.255

Asia WGS AF: 0.308 AC: 1069 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	11
Dann	Benign	0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.35		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.35		Position offset: 6

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

Publications

LitVar

Other links and lift over

dbSNP: rs12987286; hg19: chr2-148663568;