rs142187288

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_013347.4(RPA4):c.26A>G(p.Tyr9Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000144 in 1,208,082 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 51 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., 8 hem., cov: 22)

Exomes 𝑓: 0.00012 ( 0 hom. 43 hem. )

Consequence

RPA4
NM_013347.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.612

Publications

0 publications found

Variant links:

Genes affected

RPA4 (HGNC:30305): (replication protein A4) This gene encodes a single-stranded DNA-binding protein that is the 30-kDa subunit of the replication protein A complex. Replication protein A is an essential factor for DNA double-strand break repair and cell cycle checkpoint activation. The encoded protein localizes to DNA repair foci and may be involved in the cellular DNA damage response. This protein may also play a role in inhibiting viral replication.[provided by RefSeq, Apr 2010]

RPA4 links:

DIAPH2 (HGNC:2877): (diaphanous related formin 2) The product of this gene belongs to the diaphanous subfamily of the formin homology family of proteins. This gene may play a role in the development and normal function of the ovaries. Defects in this gene have been linked to premature ovarian failure 2. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

DIAPH2 Gene-Disease associations (from GenCC):

premature ovarian failure 2A
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

DIAPH2 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 (MetaRNN=0.013720214).

BS2

High Hemizygotes in GnomAd4 at 8 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013347.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RPA4	NM_013347.4	MANE Select	c.26A>G	p.Tyr9Cys	missense	Exon 1 of 1	NP_037479.1	Q13156
DIAPH2	NM_006729.5	MANE Select	c.587+2618A>G		intron	N/A	NP_006720.1	O60879-1
DIAPH2	NM_007309.4		c.587+2618A>G		intron	N/A	NP_009293.1	O60879-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RPA4	ENST00000373040.4	TSL:6 MANE Select	c.26A>G	p.Tyr9Cys	missense	Exon 1 of 1	ENSP00000362131.3	Q13156
DIAPH2	ENST00000324765.13	TSL:1 MANE Select	c.587+2618A>G		intron	N/A	ENSP00000321348.8	O60879-1
DIAPH2	ENST00000373049.8	TSL:1	c.587+2618A>G		intron	N/A	ENSP00000362140.4	O60879-2

Frequencies

GnomAD3 genomes

AF:

0.000360

AC:

AN:

111178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000917

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000288

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000170

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000172

AC:

AN:

180337

AF XY:

0.000108

show subpopulations

Gnomad AFR exome

AF:

0.000838

Gnomad AMR exome

AF:

0.000294

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000149

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000123

AC:

135

AN:

1096849

Hom.:

Cov.:

AF XY:

0.000119

AC XY:

AN XY:

362315

show subpopulations

African (AFR)

AF:

0.000948

AC:

AN:

26383

American (AMR)

AF:

0.000313

AC:

AN:

35157

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19297

East Asian (EAS)

AF:

0.00

AC:

AN:

30198

South Asian (SAS)

AF:

0.00

AC:

AN:

53879

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40465

Middle Eastern (MID)

AF:

0.00123

AC:

AN:

4073

European-Non Finnish (NFE)

AF:

0.000102

AC:

AN:

841358

Other (OTH)

AF:

0.000174

AC:

AN:

46039

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

GnomAD4 genome

AF:

0.000351

AC:

AN:

111233

Hom.:

Cov.:

AF XY:

0.000239

AC XY:

AN XY:

33449

show subpopulations

African (AFR)

AF:

0.000882

AC:

AN:

30599

American (AMR)

AF:

0.000288

AC:

AN:

10418

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2641

East Asian (EAS)

AF:

0.00

AC:

AN:

3522

South Asian (SAS)

AF:

0.00

AC:

AN:

2591

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5984

Middle Eastern (MID)

AF:

0.00

AC:

AN:

219

European-Non Finnish (NFE)

AF:

0.000170

AC:

AN:

53071

Other (OTH)

AF:

0.00

AC:

AN:

1502

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.000187

Hom.:

Bravo

AF:

0.000336

ESP6500AA

AF:

0.000782

AC:

ESP6500EA

AF:

0.000297

AC:

ExAC

AF:

0.000173

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.85

CADD

Benign

2.6

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.064

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.38

M_CAP

Benign

0.0014

MetaRNN

Benign

0.014

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.1

PhyloP100

-0.61

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.027

Sift

Benign

0.051

Sift4G

Uncertain

0.012

Polyphen

0.0050

Vest4

0.13

MVP

0.19

MPC

0.15

ClinPred

0.0050

GERP RS

-2.2

PromoterAI

-0.024

Neutral

(source)

Varity_R

0.10

gMVP

0.12

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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