2-68819201-C-T

Variant summary

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

The NM_001007231.3(ARHGAP25):​c.1082C>T​(p.Pro361Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P361T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

ARHGAP25
NM_001007231.3 missense

Scores

3
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.503
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]

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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=0.12884253).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ARHGAP25NM_001007231.3 linkc.1082C>T p.Pro361Leu missense_variant Exon 9 of 11 ENST00000409202.8 NP_001007232.2 P42331-4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ARHGAP25ENST00000409202.8 linkc.1082C>T p.Pro361Leu missense_variant Exon 9 of 11 2 NM_001007231.3 ENSP00000386911.3 P42331-4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 16, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1082C>T (p.P361L) alteration is located in exon 9 (coding exon 9) of the ARHGAP25 gene. This alteration results from a C to T substitution at nucleotide position 1082, causing the proline (P) at amino acid position 361 to be replaced by a leucine (L). 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
-0.22
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
18
DANN
Benign
0.91
Eigen
Benign
-0.24
Eigen_PC
Benign
-0.21
FATHMM_MKL
Benign
0.17
N
LIST_S2
Uncertain
0.88
D;D;D;D;D;D
M_CAP
Benign
0.0036
T
MetaRNN
Benign
0.13
T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
PrimateAI
Benign
0.45
T
PROVEAN
Uncertain
-3.3
D;D;D;D;D;D
REVEL
Benign
0.083
Sift
Benign
0.066
T;T;T;T;D;D
Sift4G
Uncertain
0.040
D;D;D;D;D;T
Polyphen
0.027
B;.;B;.;B;.
Vest4
0.064
MVP
0.31
MPC
0.27
ClinPred
0.28
T
GERP RS
5.1
gMVP
0.24

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-69046333; API