Variant chr8-144116210-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001316309.2(WDR97):c.4786C>T(p.Arg1596Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00513 in 687,756 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0041 ( 3 hom., cov: 34)

Exomes 𝑓: 0.0054 ( 13 hom. )

Consequence

WDR97
NM_001316309.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.46

Variant links:

Genes affected

WDR97 (HGNC:26959): (WD repeat domain 97) The function and protein-coding potential of this gene is unknown. The exon combination is based on AB058778.1 for which two possible open reading frames can be predicted (with start codons at nucleotide 26 or 2614). The position of the first ORF stop codon is consistent with a prediction of nonsense-mediated decay. Given the observation of the first ORF and its length, a predicted translation of the second ORF is inconsistent with the translation leaky scanning theory. Therefore, this gene is represented as a non-protein-coding transcript. [provided by RefSeq, Oct 2008]

WDR97 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007150501).

BP6

Variant 8-144116210-C-T is Benign according to our data. Variant chr8-144116210-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2658977.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00544 (2911/535446) while in subpopulation MID AF= 0.0213 (85/4000). AF 95% confidence interval is 0.0176. There are 13 homozygotes in gnomad4_exome. There are 1599 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR97	NM_001316309.2 linkuse as main transcript	c.4786C>T	p.Arg1596Cys	missense_variant	24/24	ENST00000323662.9	NP_001303238.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR97	ENST00000323662.9 linkuse as main transcript	c.4786C>T	p.Arg1596Cys	missense_variant	24/24	5	NM_001316309.2	ENSP00000320648	P1	A6NE52-1

Frequencies

GnomAD3 genomes

AF:

0.00406

AC:

618

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000917

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00360

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00457

Gnomad FIN

AF:

0.00179

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00664

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00421

AC:

499

AN:

118606

Hom.:

AF XY:

0.00458

AC XY:

299

AN XY:

65306

show subpopulations

Gnomad AFR exome

AF:

0.000345

Gnomad AMR exome

AF:

0.00299

Gnomad ASJ exome

AF:

0.00247

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00491

Gnomad FIN exome

AF:

0.00306

Gnomad NFE exome

AF:

0.00608

Gnomad OTH exome

AF:

0.00650

GnomAD4 exome

AF:

0.00544

AC:

2911

AN:

535446

Hom.:

Cov.:

AF XY:

0.00552

AC XY:

1599

AN XY:

289498

show subpopulations

Gnomad4 AFR exome

AF:

0.000802

Gnomad4 AMR exome

AF:

0.00285

Gnomad4 ASJ exome

AF:

0.00223

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00500

Gnomad4 FIN exome

AF:

0.00352

Gnomad4 NFE exome

AF:

0.00671

Gnomad4 OTH exome

AF:

0.00608

GnomAD4 genome

AF:

0.00406

AC:

618

AN:

152310

Hom.:

Cov.:

AF XY:

0.00388

AC XY:

289

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.000914

Gnomad4 AMR

AF:

0.00359

Gnomad4 ASJ

AF:

0.00432

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00457

Gnomad4 FIN

AF:

0.00179

Gnomad4 NFE

AF:

0.00664

Gnomad4 OTH

AF:

0.00616

Alfa

AF:

0.00467

Hom.:

Bravo

AF:

0.00405

TwinsUK

AF:

0.00539

AC:

ALSPAC

AF:

0.00778

AC:

ExAC

AF:

0.00285

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

Apr 01, 2023

WDR97: PP2, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.032

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.097

LIST_S2

Benign

0.72

M_CAP

Pathogenic

0.65

MetaRNN

Benign

0.0072

MetaSVM

Benign

-0.64

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.8

REVEL

Benign

0.24

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.96

Vest4

0.24

MVP

0.71

ClinPred

0.058

GERP RS

4.5

Varity_R

0.15

gMVP

0.55

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