rs17692648

Positions:

• chr2-147930162-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001616.5(ACVR2A):​c.*2888A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,358 control chromosomes in the GnomAD database, including 1,705 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 0.14 (1700 hom., cov: 31)
  • Exomes 𝑓: 0.090 (5 hom.)
• Consequence: ACVR2A NM_001616.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.531

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACVR2A	NM_001616.5	c.*2888A>C		3_prime_UTR_variant	11/11	ENST00000241416.12	NP_001607.1
ACVR2A	NM_001278579.2	c.*2888A>C		3_prime_UTR_variant	12/12		NP_001265508.1
ACVR2A	NM_001278580.2	c.*2888A>C		3_prime_UTR_variant	11/11		NP_001265509.1
ACVR2A	XM_047446292.1	c.*2888A>C		3_prime_UTR_variant	11/11		XP_047302248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACVR2A	ENST00000241416.12	c.*2888A>C		3_prime_UTR_variant	11/11	1	NM_001616.5	ENSP00000241416	P1
ACVR2A	ENST00000535787.5	c.*2888A>C		3_prime_UTR_variant	11/11	2		ENSP00000439988

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20633 AN: 151808 Hom.: 1699 Cov.: 31

Gnomad AFR AF: 0.0611

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.0971

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.0889

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.150

GnomAD4 exome AF: 0.0903 AC: 39 AN: 432 Hom.: 5 Cov.: 0 AF XY: 0.0808 AC XY: 21 AN XY: 260

Gnomad4 FIN exome AF: 0.0915

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.136 AC: 20630 AN: 151926 Hom.: 1700 Cov.: 31 AF XY: 0.132 AC XY: 9774 AN XY: 74272

Gnomad4 AFR AF: 0.0611

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.288

Gnomad4 EAS AF: 0.0967

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.0889

Gnomad4 NFE AF: 0.183

Gnomad4 OTH AF: 0.148

Alfa AF: 0.183 Hom.: 4413

Bravo AF: 0.134

Asia WGS AF: 0.121 AC: 418 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	7.6
DANN	Benign	0.74

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: rs17692648; hg19: chr2-148687731;