2-68819184-C-G

Variant names:

• chr2-68819184-C-G
• rs147150060
• NM_001007231.3:c.1065C>G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_001007231.3(ARHGAP25):​c.1065C>G​(p.Pro355Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00206 in 1,607,962 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0015 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (3 hom.)
• Consequence: ARHGAP25 NM_001007231.3 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.0740

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 Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 2-68819184-C-G is Benign according to our data. Variant chr2-68819184-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3350491.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.074 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP25	NM_001007231.3	c.1065C>G	p.Pro355Pro	synonymous_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.1065C>G	p.Pro355Pro	synonymous_variant	Exon 9 of 11	2	NM_001007231.3	ENSP00000386911.3

Frequencies

GnomAD3 genomes AF: 0.00146 AC: 222 AN: 152128 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000459

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00190

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00244

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00145 AC: 358 AN: 247380 Hom.: 1 AF XY: 0.00136 AC XY: 182 AN XY: 133724

Gnomad AFR exome AF: 0.000679

Gnomad AMR exome AF: 0.00180

Gnomad ASJ exome AF: 0.000418

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000100

Gnomad FIN exome AF: 0.000233

Gnomad NFE exome AF: 0.00235

Gnomad OTH exome AF: 0.00184

GnomAD4 exome AF: 0.00212 AC: 3085 AN: 1455716 Hom.: 3 Cov.: 31 AF XY: 0.00204 AC XY: 1480 AN XY: 723728

Gnomad4 AFR exome AF: 0.000332

Gnomad4 AMR exome AF: 0.00182

Gnomad4 ASJ exome AF: 0.000273

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000817

Gnomad4 FIN exome AF: 0.000357

Gnomad4 NFE exome AF: 0.00253

Gnomad4 OTH exome AF: 0.00242

GnomAD4 genome AF: 0.00146 AC: 222 AN: 152246 Hom.: 1 Cov.: 32 AF XY: 0.00134 AC XY: 100 AN XY: 74446

Gnomad4 AFR AF: 0.000457

Gnomad4 AMR AF: 0.00190

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000623

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00244

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00175 Hom.: 0

Bravo AF: 0.00164

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00196

EpiControl AF: 0.00202

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

ARHGAP25-related condition Benign:1

Sep 03, 2024

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	8.0
DANN	Benign	0.68

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: rs147150060; hg19: chr2-69046316;