chr2-147850239-G-C

Variant names:

• chr2-147850239-G-C
• rs1364658
• NM_001616.5:c.55+5032G>C

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+5032G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 151,798 control chromosomes in the GnomAD database, including 5,965 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 0.26 (5965 hom., cov: 31)
• Consequence: ACVR2A NM_001616.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0640
• Publications: 5 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.447 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACVR2A	NM_001616.5	MANE Select	c.55+5032G>C		intron	N/A	NP_001607.1
	ACVR2A	NM_001278579.2		c.55+5032G>C		intron	N/A	NP_001265508.1
	ACVR2A	NM_001278580.2		c.-207+5533G>C		intron	N/A	NP_001265509.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACVR2A	ENST00000241416.12	TSL:1 MANE Select	c.55+5032G>C		intron	N/A	ENSP00000241416.7
	ACVR2A	ENST00000404590.1	TSL:1	c.55+5032G>C		intron	N/A	ENSP00000384338.1
	ACVR2A	ENST00000535787.5	TSL:2	c.-207+5533G>C		intron	N/A	ENSP00000439988.1

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39500 AN: 151680 Hom.: 5969 Cov.: 31

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.462

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.295

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

GnomAD4 genome AF: 0.260 AC: 39513 AN: 151798 Hom.: 5965 Cov.: 31 AF XY: 0.263 AC XY: 19508 AN XY: 74166

African (AFR) AF: 0.107 AC: 4435 AN: 41422

American (AMR) AF: 0.309 AC: 4717 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 1092 AN: 3464

East Asian (EAS) AF: 0.462 AC: 2363 AN: 5114

South Asian (SAS) AF: 0.291 AC: 1398 AN: 4810

European-Finnish (FIN) AF: 0.335 AC: 3515 AN: 10506

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.309 AC: 21007 AN: 67920

Other (OTH) AF: 0.296 AC: 624 AN: 2110

Alfa AF: 0.284 Hom.: 821

Bravo AF: 0.257

Asia WGS AF: 0.308 AC: 1071 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.8
DANN	Benign	0.63
PhyloP100		0.064
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1364658; hg19: chr2-148607808;