Variant chr2-68813413-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001007231.3(ARHGAP25):c.801G>C(p.Glu267Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 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: 6.9e-7 ( 0 hom. )

Consequence

ARHGAP25
NM_001007231.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.881

Variant links:

Genes affected

ARHGAP25 (HGNC:28951): (Rho GTPase activating protein 25) ARHGAPs, such as ARHGAP25, encode negative regulators of Rho GTPases (see ARHA; MIM 165390), which are implicated in actin remodeling, cell polarity, and cell migration (Katoh and Katoh, 2004 [PubMed 15254788]).[supplied by OMIM, Mar 2008]

ARHGAP25 links:

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ACMG classification

Classification made for transcript

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=0.15154848).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP25	NM_001007231.3 linkuse as main transcript	c.801G>C	p.Glu267Asp	missense_variant	6/11	ENST00000409202.8	NP_001007232.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP25	ENST00000409202.8 linkuse as main transcript	c.801G>C	p.Glu267Asp	missense_variant	6/11	2	NM_001007231.3	ENSP00000386911	P1	P42331-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248732

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134548

show subpopulations

Gnomad AFR exome

AF:

0.0000618

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

6.85e-7

AC:

AN:

1459620

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726200

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 22, 2021

The c.801G>C (p.E267D) alteration is located in exon 6 (coding exon 6) of the ARHGAP25 gene. This alteration results from a G to C substitution at nucleotide position 801, causing the glutamic acid (E) at amino acid position 267 to be replaced by an aspartic acid (D). 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

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.10

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.79

T;T;T;T;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.15

T;T;T;T;T

MetaSVM

Benign

-0.89

MutationTaster

Benign

0.97

D;D;D;D;D;D;D

PrimateAI

Benign

0.43

PROVEAN

Benign

-2.0

N;N;N;N;N

REVEL

Benign

0.052

Sift

Benign

0.032

D;D;D;D;T

Sift4G

Benign

0.14

T;T;T;T;T

Polyphen

0.83

P;.;P;.;P

Vest4

0.36

MVP

0.48

MPC

0.62

ClinPred

0.30

GERP RS

2.7

gMVP

0.23

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