rs1170520147

Variant names:

• chr1-155951145-G-A
• rs1170520147
• NM_001162383.2:c.2387C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-155951145-G-A
• chr1-155951145-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001162383.2(ARHGEF2):​c.2387C>T​(p.Ala796Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000344 in 1,451,976 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: ARHGEF2 NM_001162383.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.645
• Publications: 0 publications found

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]

MIR6738 (HGNC:49939): (microRNA 6738) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.084555596).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001162383.2. 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
	ARHGEF2	NM_001162383.2	MANE Select	c.2387C>T	p.Ala796Val	missense	Exon 20 of 22	NP_001155855.1	Q92974-1
	ARHGEF2	NM_001162384.2		c.2384C>T	p.Ala795Val	missense	Exon 20 of 22	NP_001155856.1	Q92974-2
	ARHGEF2	NM_001350112.2		c.2333C>T	p.Ala778Val	missense	Exon 20 of 22	NP_001337041.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF2	ENST00000361247.9	TSL:1 MANE Select	c.2387C>T	p.Ala796Val	missense	Exon 20 of 22	ENSP00000354837.4	Q92974-1
	ARHGEF2	ENST00000313667.8	TSL:1	c.2384C>T	p.Ala795Val	missense	Exon 20 of 22	ENSP00000314787.4	Q92974-2
	ARHGEF2	ENST00000313695.11	TSL:1	c.2303C>T	p.Ala768Val	missense	Exon 20 of 22	ENSP00000315325.7	Q92974-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000450 AC: 1 AN: 222328 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000307

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000344 AC: 5 AN: 1451976 Hom.: 0 Cov.: 32 AF XY: 0.00000554 AC XY: 4 AN XY: 721938

African (AFR) AF: 0.00 AC: 0 AN: 33382

American (AMR) AF: 0.0000689 AC: 3 AN: 43542

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25918

East Asian (EAS) AF: 0.00 AC: 0 AN: 39386

South Asian (SAS) AF: 0.00 AC: 0 AN: 85152

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49766

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1109048

Other (OTH) AF: 0.0000167 AC: 1 AN: 60034

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.029	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.085	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.65
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.55	N
REVEL	Benign	0.063
Sift	Benign	0.065	T
Sift4G	Benign	0.27	T
Polyphen		0.0010	B
Vest4		0.10
MVP		0.22
MPC		0.50
ClinPred		0.061	T
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.030
gMVP		0.13
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1170520147; hg19: chr1-155920936; COSMIC: COSV107377365;