NM_001616.5:c.55+24752C>A

Variant names:

• chr2-147869959-C-A
• rs929939
• NM_001616.5:c.55+24752C>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.55+24752C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 151,220 control chromosomes in the GnomAD database, including 8,474 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 0.33 (8474 hom., cov: 29)
• Consequence: ACVR2A NM_001616.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0670
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.507 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.55+24752C>A		intron	N/A	NP_001607.1	P27037-1
	ACVR2A	NM_001278579.2		c.55+24752C>A		intron	N/A	NP_001265508.1	P27037-1
	ACVR2A	NM_001278580.2		c.-207+25253C>A		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.55+24752C>A		intron	N/A	ENSP00000241416.7	P27037-1
	ACVR2A	ENST00000404590.1	TSL:1	c.55+24752C>A		intron	N/A	ENSP00000384338.1	P27037-1
	ACVR2A	ENST00000943648.1		c.55+24752C>A		intron	N/A	ENSP00000613707.1

Frequencies

GnomAD3 genomes AF: 0.330 AC: 49872 AN: 151100 Hom.: 8469 Cov.: 29

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.423

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.330 AC: 49920 AN: 151220 Hom.: 8474 Cov.: 29 AF XY: 0.332 AC XY: 24488 AN XY: 73810

African (AFR) AF: 0.303 AC: 12487 AN: 41160

American (AMR) AF: 0.385 AC: 5838 AN: 15168

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1141 AN: 3466

East Asian (EAS) AF: 0.523 AC: 2661 AN: 5086

South Asian (SAS) AF: 0.322 AC: 1539 AN: 4780

European-Finnish (FIN) AF: 0.339 AC: 3538 AN: 10444

Middle Eastern (MID) AF: 0.414 AC: 121 AN: 292

European-Non Finnish (NFE) AF: 0.319 AC: 21607 AN: 67814

Other (OTH) AF: 0.353 AC: 742 AN: 2104

Alfa AF: 0.324 Hom.: 1326

Bravo AF: 0.337

Asia WGS AF: 0.361 AC: 1257 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.35
PhyloP100		0.067
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: rs929939; hg19: chr2-148627528; COSMIC: COSV54021637;