rs2364403

Variant names:

• chr1-155957961-G-A
• rs2364403
• NM_001162383.2:c.1546-79C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-155957961-G-A
• chr1-155957961-G-C
• chr1-155957961-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001162383.2(ARHGEF2):​c.1546-79C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 1,432,420 control chromosomes in the GnomAD database, including 48,704 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 (6104 hom., cov: 33)
  • Exomes 𝑓: 0.23 (42600 hom.)
• Consequence: ARHGEF2 NM_001162383.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.587
• Publications: 19 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]

ARHGEF2 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with midbrain and hindbrain malformations

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

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.1546-79C>T		intron	N/A	NP_001155855.1	Q92974-1
	ARHGEF2	NM_001162384.2		c.1543-79C>T		intron	N/A	NP_001155856.1	Q92974-2
	ARHGEF2	NM_001350112.2		c.1492-79C>T		intron	N/A	NP_001337041.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF2	ENST00000361247.9	TSL:1 MANE Select	c.1546-79C>T		intron	N/A	ENSP00000354837.4	Q92974-1
	ARHGEF2	ENST00000313667.8	TSL:1	c.1543-79C>T		intron	N/A	ENSP00000314787.4	Q92974-2
	ARHGEF2	ENST00000313695.11	TSL:1	c.1462-79C>T		intron	N/A	ENSP00000315325.7	Q92974-3

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39509 AN: 152044 Hom.: 6092 Cov.: 33

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.775

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.263

GnomAD4 exome AF: 0.234 AC: 299159 AN: 1280258 Hom.: 42600 AF XY: 0.234 AC XY: 147807 AN XY: 633004

African (AFR) AF: 0.292 AC: 8643 AN: 29566

American (AMR) AF: 0.395 AC: 12119 AN: 30714

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 4208 AN: 21006

East Asian (EAS) AF: 0.787 AC: 29204 AN: 37112

South Asian (SAS) AF: 0.285 AC: 19829 AN: 69684

European-Finnish (FIN) AF: 0.193 AC: 8910 AN: 46062

Middle Eastern (MID) AF: 0.185 AC: 934 AN: 5048

European-Non Finnish (NFE) AF: 0.204 AC: 201616 AN: 987106

Other (OTH) AF: 0.254 AC: 13696 AN: 53960

GnomAD4 genome AF: 0.260 AC: 39543 AN: 152162 Hom.: 6104 Cov.: 33 AF XY: 0.263 AC XY: 19594 AN XY: 74406

African (AFR) AF: 0.288 AC: 11961 AN: 41474

American (AMR) AF: 0.298 AC: 4556 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 690 AN: 3468

East Asian (EAS) AF: 0.775 AC: 4006 AN: 5168

South Asian (SAS) AF: 0.301 AC: 1452 AN: 4826

European-Finnish (FIN) AF: 0.194 AC: 2060 AN: 10606

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14045 AN: 68012

Other (OTH) AF: 0.259 AC: 547 AN: 2110

Alfa AF: 0.233 Hom.: 12526

Bravo AF: 0.276

Asia WGS AF: 0.512 AC: 1779 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.1
DANN	Benign	0.23
PhyloP100		0.59
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: rs2364403; hg19: chr1-155927752; COSMIC: COSV58112732; COSMIC: COSV58112732;