chr2-147890490-A-G

Variant names:

• chr2-147890490-A-G
• rs10497024
• NM_001616.5:c.56-5811A>G

Variant summary

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

The NM_001616.5(ACVR2A):​c.56-5811A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 152,014 control chromosomes in the GnomAD database, including 5,970 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 (5970 hom., cov: 31)
• Consequence: ACVR2A NM_001616.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.114
• Publications: 4 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.445 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACVR2A	NM_001616.5	MANE Select	c.56-5811A>G		intron	N/A	NP_001607.1	P27037-1
	ACVR2A	NM_001278579.2		c.56-5811A>G		intron	N/A	NP_001265508.1	P27037-1
	ACVR2A	NM_001278580.2		c.-206-5874A>G		intron	N/A	NP_001265509.1	P27037-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACVR2A	ENST00000241416.12	TSL:1 MANE Select	c.56-5811A>G		intron	N/A	ENSP00000241416.7	P27037-1
	ACVR2A	ENST00000404590.1	TSL:1	c.56-5811A>G		intron	N/A	ENSP00000384338.1	P27037-1
	ACVR2A	ENST00000943648.1		c.56-5811A>G		intron	N/A	ENSP00000613707.1

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39539 AN: 151894 Hom.: 5974 Cov.: 31

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.295

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

GnomAD4 genome AF: 0.260 AC: 39552 AN: 152014 Hom.: 5970 Cov.: 31 AF XY: 0.263 AC XY: 19538 AN XY: 74284

African (AFR) AF: 0.107 AC: 4433 AN: 41488

American (AMR) AF: 0.309 AC: 4724 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 1095 AN: 3462

East Asian (EAS) AF: 0.461 AC: 2381 AN: 5166

South Asian (SAS) AF: 0.290 AC: 1394 AN: 4812

European-Finnish (FIN) AF: 0.335 AC: 3528 AN: 10538

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.309 AC: 21015 AN: 67964

Other (OTH) AF: 0.295 AC: 622 AN: 2110

Alfa AF: 0.278 Hom.: 830

Bravo AF: 0.257

Asia WGS AF: 0.307 AC: 1065 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.5
DANN	Benign	0.80
PhyloP100		-0.11
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: rs10497024; hg19: chr2-148648059;