2-147901026-G-C

Variant names:

• chr2-147901026-G-C
• rs3754541
• NM_001616.5:c.528+1128G>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001616.5(ACVR2A):​c.528+1128G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000895 in 151,914 control chromosomes in the GnomAD database, including 1 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 0.00090 (1 hom., cov: 32)
• Consequence: ACVR2A NM_001616.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.128
• Publications: 2 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]

ENSG00000223911 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BS2: High AC in GnomAd4 at 136 AD gene.

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.528+1128G>C		intron	N/A	NP_001607.1
	ACVR2A	NM_001278579.2		c.528+1128G>C		intron	N/A	NP_001265508.1
	ACVR2A	NM_001278580.2		c.204+1128G>C		intron	N/A	NP_001265509.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACVR2A	ENST00000241416.12	TSL:1 MANE Select	c.528+1128G>C		intron	N/A	ENSP00000241416.7
	ACVR2A	ENST00000404590.1	TSL:1	c.528+1128G>C		intron	N/A	ENSP00000384338.1
	ACVR2A	ENST00000943648.1		c.528+1128G>C		intron	N/A	ENSP00000613707.1

Frequencies

GnomAD3 genomes AF: 0.000896 AC: 136 AN: 151796 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00191

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00352

Gnomad FIN AF: 0.0000945

Gnomad MID AF: 0.0160

Gnomad NFE AF: 0.000796

Gnomad OTH AF: 0.00674

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

GnomAD4 genome AF: 0.000895 AC: 136 AN: 151914 Hom.: 1 Cov.: 32 AF XY: 0.00101 AC XY: 75 AN XY: 74252

African (AFR) AF: 0.000337 AC: 14 AN: 41490

American (AMR) AF: 0.00190 AC: 29 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.00353 AC: 17 AN: 4820

European-Finnish (FIN) AF: 0.0000945 AC: 1 AN: 10580

Middle Eastern (MID) AF: 0.0172 AC: 5 AN: 290

European-Non Finnish (NFE) AF: 0.000796 AC: 54 AN: 67848

Other (OTH) AF: 0.00667 AC: 14 AN: 2100

Alfa AF: 0.00 Hom.: 68

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.8
DANN	Benign	0.57
PhyloP100		0.13

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: rs3754541; hg19: chr2-148658595;