2-147899548-G-C

Variant names:

• chr2-147899548-G-C
• NM_001616.5:c.354G>C
• ACVR2A p.Pro118Pro

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001616.5(ACVR2A):​c.354G>C​(p.Pro118Pro) variant causes a synonymous 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: 31)
• Consequence: ACVR2A NM_001616.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.673
• Publications: 0 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP7: Synonymous conserved (PhyloP=-0.673 with no splicing effect.

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.354G>C	p.Pro118Pro	synonymous	Exon 3 of 11	NP_001607.1	P27037-1
	ACVR2A	NM_001278579.2		c.354G>C	p.Pro118Pro	synonymous	Exon 4 of 12	NP_001265508.1	P27037-1
	ACVR2A	NM_001278580.2		c.30G>C	p.Pro10Pro	synonymous	Exon 3 of 11	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.354G>C	p.Pro118Pro	synonymous	Exon 3 of 11	ENSP00000241416.7	P27037-1
	ACVR2A	ENST00000404590.1	TSL:1	c.354G>C	p.Pro118Pro	synonymous	Exon 4 of 12	ENSP00000384338.1	P27037-1
	ACVR2A	ENST00000943648.1		c.354G>C	p.Pro118Pro	synonymous	Exon 3 of 12	ENSP00000613707.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	6.5
DANN	Benign	0.71
PhyloP100		-0.67
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr2-148657117;