chr2-68782239-A-G

Position:

• chr2-68782239-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001007231.3(ARHGAP25):​c.268A>G​(p.Met90Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,770 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 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: 0.0000027 (0 hom.)
• Consequence: ARHGAP25 NM_001007231.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.30

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=0.14341038).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP25	NM_001007231.3	c.268A>G	p.Met90Val	missense_variant	3/11	ENST00000409202.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP25	ENST00000409202.8	c.268A>G	p.Met90Val	missense_variant	3/11	2	NM_001007231.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461770 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727198

Gnomad4 AFR exome AF: 0.00

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.063	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	8.6
DANN	Benign	0.96
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.33
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.67	T;T;T;T;T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.14	T;T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.50	N;N;.;.;.
MutationTaster	Benign	0.90	D;D;D;D;D;D;D
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.73	N;N;N;N;N
REVEL	Benign	0.13
Sift	Uncertain	0.0090	D;D;D;D;T
Sift4G	Benign	0.15	T;D;T;T;T
Polyphen		0.0020	B;.;B;.;B
Vest4		0.16
MutPred		0.51		Loss of disorder (P = 0.1263);Loss of disorder (P = 0.1263);.;.;.;
MVP		0.58
MPC		0.26
ClinPred		0.59	D
GERP RS		4.6
gMVP		0.20

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

Other links and lift over

dbSNP: rs1678391481; hg19: chr2-69009371;