Variant 1-155951747-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_001162383.2(ARHGEF2):c.2202G>T(p.Pro734Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00233 in 1,614,032 control chromosomes in the GnomAD database, including 86 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 51 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 35 hom. )

Consequence

ARHGEF2
NM_001162383.2 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.142

Variant links:

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 links:

ARHGEF2 (HGNC:):

ARHGEF2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 1-155951747-C-A is Benign according to our data. Variant chr1-155951747-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 777949.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0126 (1923/152212) while in subpopulation AFR AF= 0.0441 (1831/41516). AF 95% confidence interval is 0.0424. There are 51 homozygotes in gnomad4. There are 917 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 51 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF2	NM_001162383.2 linkuse as main transcript	c.2202G>T	p.Pro734Pro	synonymous_variant	18/22	ENST00000361247.9	NP_001155855.1	Q92974-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGEF2	ENST00000361247.9 linkuse as main transcript	c.2202G>T	p.Pro734Pro	synonymous_variant	18/22	1	NM_001162383.2	ENSP00000354837.4		Q92974-1

Frequencies

GnomAD3 genomes

AF:

0.0126

AC:

1922

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0442

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00406

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00909

GnomAD3 exomes

AF:

0.00313

AC:

786

AN:

251304

Hom.:

AF XY:

0.00247

AC XY:

335

AN XY:

135848

show subpopulations

Gnomad AFR exome

AF:

0.0443

Gnomad AMR exome

AF:

0.00104

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000185

Gnomad OTH exome

AF:

0.00130

GnomAD4 exome

AF:

0.00125

AC:

1831

AN:

1461820

Hom.:

Cov.:

AF XY:

0.00109

AC XY:

792

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.0447

Gnomad4 AMR exome

AF:

0.00148

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000928

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000890

Gnomad4 OTH exome

AF:

0.00262

GnomAD4 genome

AF:

0.0126

AC:

1923

AN:

152212

Hom.:

Cov.:

AF XY:

0.0123

AC XY:

917

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0441

Gnomad4 AMR

AF:

0.00406

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00900

Alfa

AF:

0.00512

Hom.:

Bravo

AF:

0.0141

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000237

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Neurodevelopmental disorder with midbrain and hindbrain malformations

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Aug 13, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.57

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over