Genetic Variant ARHGAP25:p.Pro355Pro (chr2-68819184-C-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_ModerateBP6BP7BS2

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

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.0740

Publications

1 publications found

Variant links:

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]

ARHGAP25 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.124).

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 VariationId 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

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARHGAP25	NM_001007231.3	MANE Select	c.1065C>G	p.Pro355Pro	synonymous	Exon 9 of 11	NP_001007232.2	P42331-4
ARHGAP25	NM_001364819.1		c.1062C>G	p.Pro354Pro	synonymous	Exon 9 of 11	NP_001351748.1	P42331-1
ARHGAP25	NM_001166276.2		c.1044C>G	p.Pro348Pro	synonymous	Exon 8 of 10	NP_001159748.1	P42331-6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARHGAP25	ENST00000409202.8	TSL:2 MANE Select	c.1065C>G	p.Pro355Pro	synonymous	Exon 9 of 11	ENSP00000386911.3	P42331-4
ARHGAP25	ENST00000409220.5	TSL:1	c.1044C>G	p.Pro348Pro	synonymous	Exon 8 of 10	ENSP00000386241.1	P42331-6
ARHGAP25	ENST00000409030.7	TSL:1	c.1041C>G	p.Pro347Pro	synonymous	Exon 8 of 10	ENSP00000386863.3	P42331-3

Frequencies

GnomAD3 genomes

AF:

0.00146

AC:

222

AN:

152128

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.00145

AC:

358

AN:

247380

AF XY:

0.00136

show subpopulations

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 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.:

Cov.:

AF XY:

0.00204

AC XY:

1480

AN XY:

723728

show subpopulations

African (AFR)

AF:

0.000332

AC:

AN:

33160

American (AMR)

AF:

0.00182

AC:

AN:

43928

Ashkenazi Jewish (ASJ)

AF:

0.000273

AC:

AN:

25626

East Asian (EAS)

AF:

0.00

AC:

AN:

39632

South Asian (SAS)

AF:

0.0000817

AC:

AN:

85650

European-Finnish (FIN)

AF:

0.000357

AC:

AN:

53270

Middle Eastern (MID)

AF:

0.00245

AC:

AN:

5710

European-Non Finnish (NFE)

AF:

0.00253

AC:

2802

AN:

1108706

Other (OTH)

AF:

0.00242

AC:

145

AN:

60034

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

151

303

454

606

757

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

204

306

408

510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00146

AC:

222

AN:

152246

Hom.:

Cov.:

AF XY:

0.00134

AC XY:

100

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.000457

AC:

AN:

41548

American (AMR)

AF:

0.00190

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.000623

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00244

AC:

166

AN:

68018

Other (OTH)

AF:

0.00142

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00175

Hom.:

Bravo

AF:

0.00164

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00196

EpiControl

AF:

0.00202

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

ARHGAP25-related condition (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

8.0

(source)

DANN

Benign

0.68

PhyloP100

-0.074

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over