rs6713811

Positions:

• chr2-147873966-G-A
• chr2-147873966-G-T

Variant summary

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

The NM_001616.5(ACVR2A):​c.56-22335G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 151,746 control chromosomes in the GnomAD database, including 11,887 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 0.39 (11887 hom., cov: 32)
• Consequence: ACVR2A NM_001616.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.377

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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACVR2A	NM_001616.5	c.56-22335G>A		intron_variant		ENST00000241416.12
ACVR2A	NM_001278579.2	c.56-22335G>A		intron_variant
ACVR2A	NM_001278580.2	c.-206-22398G>A		intron_variant
ACVR2A	XM_047446292.1	c.-269-22335G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACVR2A	ENST00000241416.12	c.56-22335G>A		intron_variant		1	NM_001616.5	P1

Frequencies

GnomAD3 genomes AF: 0.388 AC: 58783 AN: 151628 Hom.: 11874 Cov.: 32

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.503

Gnomad FIN AF: 0.554

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.352

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

GnomAD4 genome AF: 0.388 AC: 58835 AN: 151746 Hom.: 11887 Cov.: 32 AF XY: 0.397 AC XY: 29410 AN XY: 74162

Gnomad4 AFR AF: 0.282

Gnomad4 AMR AF: 0.399

Gnomad4 ASJ AF: 0.285

Gnomad4 EAS AF: 0.379

Gnomad4 SAS AF: 0.503

Gnomad4 FIN AF: 0.554

Gnomad4 NFE AF: 0.423

Gnomad4 OTH AF: 0.357

Alfa AF: 0.404 Hom.: 2154

Bravo AF: 0.365

Asia WGS AF: 0.476 AC: 1653 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.44
DANN	Benign	0.58

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: rs6713811; hg19: chr2-148631535;