Variant X-96881646-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_006729.5(DIAPH2):c.515C>T(p.Ser172Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000257 in 1,204,405 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 13 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000036 ( 0 hom., 3 hem., cov: 23)

Exomes 𝑓: 0.000025 ( 0 hom. 10 hem. )

Consequence

DIAPH2
NM_006729.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.48

Variant links:

Genes affected

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6

Variant X-96881646-C-T is Benign according to our data. Variant chrX-96881646-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2661020.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIAPH2	NM_006729.5 linkuse as main transcript	c.515C>T	p.Ser172Leu	missense_variant	5/27	ENST00000324765.13	NP_006720.1
DIAPH2	NM_007309.4 linkuse as main transcript	c.515C>T	p.Ser172Leu	missense_variant	5/27		NP_009293.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DIAPH2	ENST00000324765.13 linkuse as main transcript	c.515C>T	p.Ser172Leu	missense_variant	5/27	1	NM_006729.5	ENSP00000321348	A2	O60879-1
DIAPH2	ENST00000373049.8 linkuse as main transcript	c.515C>T	p.Ser172Leu	missense_variant	5/27	1		ENSP00000362140	P3	O60879-2

Frequencies

GnomAD3 genomes

AF:

0.0000359

AC:

AN:

111499

Hom.:

Cov.:

AF XY:

0.0000890

AC XY:

AN XY:

33693

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00112

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000887

AC:

AN:

180427

Hom.:

AF XY:

0.0000615

AC XY:

AN XY:

65051

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000376

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00103

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000247

AC:

AN:

1092859

Hom.:

Cov.:

AF XY:

0.0000279

AC XY:

AN XY:

358575

show subpopulations

Gnomad4 AFR exome

AF:

0.0000381

Gnomad4 AMR exome

AF:

0.0000287

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000599

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000596

Gnomad4 OTH exome

AF:

0.0000436

GnomAD4 genome

AF:

0.0000359

AC:

AN:

111546

Hom.:

Cov.:

AF XY:

0.0000889

AC XY:

AN XY:

33750

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00113

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000642

ExAC

AF:

0.0000906

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

DIAPH2: PP3, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Uncertain

0.046

BayesDel_noAF

Pathogenic

0.24

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.87

.;.;.;D;D

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

D;D;D;D;D

M_CAP

Pathogenic

0.76

MetaRNN

Uncertain

0.44

T;T;T;T;T

MetaSVM

Uncertain

0.77

MutationAssessor

Benign

2.0

.;.;M;M;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Pathogenic

0.85

PROVEAN

Uncertain

-3.5

D;D;D;D;.

REVEL

Pathogenic

0.81

Sift

Benign

0.035

D;D;D;D;.

Sift4G

Benign

0.072

T;T;T;T;T

Polyphen

1.0, 0.97

.;.;D;D;.

Vest4

0.73

MutPred

0.42

Loss of disorder (P = 0.0085);Loss of disorder (P = 0.0085);Loss of disorder (P = 0.0085);Loss of disorder (P = 0.0085);.;

MVP

0.93

MPC

0.29

ClinPred

0.23

GERP RS

5.4

Varity_R

0.61

gMVP

0.59

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over