NM_001162383.2:c.2472A>G

Variant names:

• chr1-155951060-T-C
• rs1379606484
• NM_001162383.2:c.2472A>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001162383.2(ARHGEF2):​c.2472A>G​(p.Leu824Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,448,158 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ARHGEF2 NM_001162383.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.986
• 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 1-155951060-T-C is Benign according to our data. Variant chr1-155951060-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2672361.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.986 with no splicing effect.

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.2472A>G	p.Leu824Leu	synonymous	Exon 20 of 22	NP_001155855.1	Q92974-1
	ARHGEF2	NM_001162384.2		c.2469A>G	p.Leu823Leu	synonymous	Exon 20 of 22	NP_001155856.1	Q92974-2
	ARHGEF2	NM_001350112.2		c.2418A>G	p.Leu806Leu	synonymous	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.2472A>G	p.Leu824Leu	synonymous	Exon 20 of 22	ENSP00000354837.4	Q92974-1
	ARHGEF2	ENST00000313667.8	TSL:1	c.2469A>G	p.Leu823Leu	synonymous	Exon 20 of 22	ENSP00000314787.4	Q92974-2
	ARHGEF2	ENST00000313695.11	TSL:1	c.2388A>G	p.Leu796Leu	synonymous	Exon 20 of 22	ENSP00000315325.7	Q92974-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 217862 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 6.91e-7 AC: 1 AN: 1448158 Hom.: 0 Cov.: 32 AF XY: 0.00000139 AC XY: 1 AN XY: 719982

African (AFR) AF: 0.00 AC: 0 AN: 33240

American (AMR) AF: 0.00 AC: 0 AN: 42870

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25842

East Asian (EAS) AF: 0.00 AC: 0 AN: 39110

South Asian (SAS) AF: 0.00 AC: 0 AN: 85148

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48918

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1107444

Other (OTH) AF: 0.00 AC: 0 AN: 59846

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.54
DANN	Benign	0.43
PhyloP100		-0.99
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Mutation Taster		=100/0	polymorphism

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: rs1379606484; hg19: chr1-155920851;