2-68807464-C-A

Variant names:

• chr2-68807464-C-A
• rs958078986
• NM_001007231.3:c.658C>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001007231.3(ARHGAP25):​c.658C>A​(p.Arg220Arg) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ARHGAP25 NM_001007231.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.86
• Publications: 1 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.148).
• BP7: Synonymous conserved (PhyloP=1.86 with no splicing effect.

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.658C>A	p.Arg220Arg	synonymous	Exon 5 of 11	NP_001007232.2	P42331-4
	ARHGAP25	NM_001364819.1		c.655C>A	p.Arg219Arg	synonymous	Exon 5 of 11	NP_001351748.1	P42331-1
	ARHGAP25	NM_001166276.2		c.637C>A	p.Arg213Arg	synonymous	Exon 4 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.658C>A	p.Arg220Arg	synonymous	Exon 5 of 11	ENSP00000386911.3	P42331-4
	ARHGAP25	ENST00000409220.5	TSL:1	c.637C>A	p.Arg213Arg	synonymous	Exon 4 of 10	ENSP00000386241.1	P42331-6
	ARHGAP25	ENST00000409030.7	TSL:1	c.634C>A	p.Arg212Arg	synonymous	Exon 4 of 10	ENSP00000386863.3	P42331-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.18
CADD	Benign	8.8
DANN	Benign	0.71
PhyloP100		1.9
PromoterAI		-0.00030	Neutral
Mutation Taster		=100/0	polymorphism

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

dbSNP: rs958078986; hg19: chr2-69034596;