chr2-147901026-G-A

Variant names:

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

Variant summary

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

The NM_001616.5(ACVR2A):​c.528+1128G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 151,880 control chromosomes in the GnomAD database, including 1,913 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 (1913 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.191 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.528+1128G>A		intron	N/A	NP_001607.1
	ACVR2A	NM_001278579.2		c.528+1128G>A		intron	N/A	NP_001265508.1
	ACVR2A	NM_001278580.2		c.204+1128G>A		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>A		intron	N/A	ENSP00000241416.7
	ACVR2A	ENST00000404590.1	TSL:1	c.528+1128G>A		intron	N/A	ENSP00000384338.1
	ACVR2A	ENST00000943648.1		c.528+1128G>A		intron	N/A	ENSP00000613707.1

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21694 AN: 151762 Hom.: 1914 Cov.: 32

Gnomad AFR AF: 0.0634

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.0987

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.0905

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.143 AC: 21687 AN: 151880 Hom.: 1913 Cov.: 32 AF XY: 0.138 AC XY: 10245 AN XY: 74236

African (AFR) AF: 0.0634 AC: 2630 AN: 41482

American (AMR) AF: 0.130 AC: 1978 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 1122 AN: 3466

East Asian (EAS) AF: 0.0983 AC: 509 AN: 5178

South Asian (SAS) AF: 0.152 AC: 731 AN: 4816

European-Finnish (FIN) AF: 0.0905 AC: 957 AN: 10580

Middle Eastern (MID) AF: 0.224 AC: 65 AN: 290

European-Non Finnish (NFE) AF: 0.194 AC: 13150 AN: 67832

Other (OTH) AF: 0.153 AC: 321 AN: 2100

Alfa AF: 0.0623 Hom.: 68

Bravo AF: 0.141

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.2
DANN	Benign	0.61
PhyloP100		0.13
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: rs3754541; hg19: chr2-148658595;