2-147929492-A-T

Variant names:

• chr2-147929492-A-T
• rs13430086
• NM_001616.5:c.*2218A>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.*2218A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 152,284 control chromosomes in the GnomAD database, including 8,453 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 0.30 (8404 hom., cov: 31)
  • Exomes 𝑓: 0.51 (49 hom.)
• Consequence: ACVR2A NM_001616.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66
• Publications: 14 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=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001616.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACVR2A	NM_001616.5	MANE Select	c.*2218A>T		3_prime_UTR	Exon 11 of 11	NP_001607.1
	ACVR2A	NM_001278579.2		c.*2218A>T		3_prime_UTR	Exon 12 of 12	NP_001265508.1
	ACVR2A	NM_001278580.2		c.*2218A>T		3_prime_UTR	Exon 11 of 11	NP_001265509.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACVR2A	ENST00000241416.12	TSL:1 MANE Select	c.*2218A>T		3_prime_UTR	Exon 11 of 11	ENSP00000241416.7
	ACVR2A	ENST00000535787.5	TSL:2	c.*2218A>T		3_prime_UTR	Exon 11 of 11	ENSP00000439988.1

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45575 AN: 151798 Hom.: 8394 Cov.: 31

Gnomad AFR AF: 0.0876

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.511

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.270

GnomAD4 exome AF: 0.514 AC: 189 AN: 368 Hom.: 49 Cov.: 0 AF XY: 0.541 AC XY: 120 AN XY: 222

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.517 AC: 187 AN: 362

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AF: 0.250 AC: 1 AN: 4

GnomAD4 genome AF: 0.300 AC: 45603 AN: 151916 Hom.: 8404 Cov.: 31 AF XY: 0.312 AC XY: 23147 AN XY: 74226

African (AFR) AF: 0.0874 AC: 3628 AN: 41528

American (AMR) AF: 0.340 AC: 5163 AN: 15194

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 796 AN: 3470

East Asian (EAS) AF: 0.379 AC: 1961 AN: 5176

South Asian (SAS) AF: 0.468 AC: 2256 AN: 4818

European-Finnish (FIN) AF: 0.511 AC: 5379 AN: 10528

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.375 AC: 25433 AN: 67888

Other (OTH) AF: 0.275 AC: 581 AN: 2110

Alfa AF: 0.330 Hom.: 1191

Bravo AF: 0.272

Asia WGS AF: 0.448 AC: 1541 AN: 3446

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.022
DANN	Benign	0.46
PhyloP100		-1.7
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: rs13430086; hg19: chr2-148687061;