1-155950465-G-T

Variant names:

• chr1-155950465-G-T
• rs1675179897
• NM_001162383.2:c.2721C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001162383.2(ARHGEF2):​c.2721C>A​(p.Asp907Glu) variant causes a missense 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARHGEF2 NM_001162383.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.197

Genes affected

ARHGEF2 (HGNC:682): (Rho/Rac guanine nucleotide exchange factor 2) Rho GTPases play a fundamental role in numerous cellular processes that are initiated by extracellular stimuli that work through G protein coupled receptors. The encoded protein may form complex with G proteins and stimulate rho-dependent signals. Alternatively spliced transcript variants encoding different isoforms have been identified.[provided by RefSeq, Jun 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.093098044).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGEF2	NM_001162383.2	c.2721C>A	p.Asp907Glu	missense_variant	Exon 21 of 22	ENST00000361247.9	NP_001155855.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGEF2	ENST00000361247.9	c.2721C>A	p.Asp907Glu	missense_variant	Exon 21 of 22	1	NM_001162383.2	ENSP00000354837.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2721C>A (p.D907E) alteration is located in exon 21 (coding exon 21) of the ARHGEF2 gene. This alteration results from a C to A substitution at nucleotide position 2721, causing the aspartic acid (D) at amino acid position 907 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.017	.;T;T;.
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.31
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.71	T;T;T;T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.093	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	.;L;.;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	0.28	N;N;.;N
REVEL	Benign	0.079
Sift	Benign	0.32	T;T;.;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.0, 0.0010	.;B;.;B
Vest4		0.14
MVP		0.48
MPC		0.44
ClinPred		0.12	T
GERP RS		3.5
Varity_R		0.055
gMVP		0.15

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1675179897; hg19: chr1-155920256;