chr2-147927404-C-A

Variant names:

• chr2-147927404-C-A
• rs1803029
• NM_001616.5:c.*130C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001616.5(ACVR2A):​c.*130C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ACVR2A NM_001616.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.695
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACVR2A	NM_001616.5	MANE Select	c.*130C>A		3_prime_UTR	Exon 11 of 11	NP_001607.1
	ACVR2A	NM_001278579.2		c.*130C>A		3_prime_UTR	Exon 12 of 12	NP_001265508.1
	ACVR2A	NM_001278580.2		c.*130C>A		3_prime_UTR	Exon 11 of 11	NP_001265509.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACVR2A	ENST00000241416.12	TSL:1 MANE Select	c.*130C>A		3_prime_UTR	Exon 11 of 11	ENSP00000241416.7
	ACVR2A	ENST00000404590.1	TSL:1	c.*130C>A		3_prime_UTR	Exon 12 of 12	ENSP00000384338.1
	ACVR2A	ENST00000943648.1		c.*130C>A		3_prime_UTR	Exon 12 of 12	ENSP00000613707.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 763766 Hom.: 0 Cov.: 10 AF XY: 0.00 AC XY: 0 AN XY: 386274

African (AFR) AF: 0.00 AC: 0 AN: 16508

American (AMR) AF: 0.00 AC: 0 AN: 14772

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15212

East Asian (EAS) AF: 0.00 AC: 0 AN: 30258

South Asian (SAS) AF: 0.00 AC: 0 AN: 46612

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32432

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3674

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 568356

Other (OTH) AF: 0.00 AC: 0 AN: 35942

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	4.9
DANN	Benign	0.86
PhyloP100		-0.69

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: rs1803029; hg19: chr2-148684973;