2-68819201-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 14/20 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12884253).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001007231.3. 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
	ARHGAP25	NM_001007231.3	MANE Select	c.1082C>T	p.Pro361Leu	missense	Exon 9 of 11	NP_001007232.2	P42331-4
	ARHGAP25	NM_001364819.1		c.1079C>T	p.Pro360Leu	missense	Exon 9 of 11	NP_001351748.1	P42331-1
	ARHGAP25	NM_001166276.2		c.1061C>T	p.Pro354Leu	missense	Exon 8 of 10	NP_001159748.1	P42331-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP25	ENST00000409202.8	TSL:2 MANE Select	c.1082C>T	p.Pro361Leu	missense	Exon 9 of 11	ENSP00000386911.3	P42331-4
	ARHGAP25	ENST00000409220.5	TSL:1	c.1061C>T	p.Pro354Leu	missense	Exon 8 of 10	ENSP00000386241.1	P42331-6
	ARHGAP25	ENST00000409030.7	TSL:1	c.1058C>T	p.Pro353Leu	missense	Exon 8 of 10	ENSP00000386863.3	P42331-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
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
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.50
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.083
Sift	Benign	0.066	T
Sift4G	Uncertain	0.040	D
Polyphen		0.027	B
Vest4		0.064
MVP		0.31
MPC		0.27
ClinPred		0.28	T
GERP RS		5.1
gMVP		0.24
Mutation Taster		=45/55	disease causing

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

hg19: chr2-69046333;