2-68819201-C-T

Variant names:

• chr2-68819201-C-T
• NM_001007231.3:c.1082C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.503

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]

ACMG classification

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
ARHGAP25	NM_001007231.3	c.1082C>T	p.Pro361Leu	missense_variant	Exon 9 of 11	ENST00000409202.8	NP_001007232.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP25	ENST00000409202.8	c.1082C>T	p.Pro361Leu	missense_variant	Exon 9 of 11	2	NM_001007231.3	ENSP00000386911.3

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

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;