Variant 18-56685981-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_015285.3(WDR7):c.546G>A(p.Val182=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00649 in 1,602,130 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0041 ( 3 hom., cov: 31)

Exomes 𝑓: 0.0067 ( 47 hom. )

Consequence

WDR7
NM_015285.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.22

Variant links:

Genes affected

WDR7 (HGNC:13490): (WD repeat domain 7) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD) that may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. The encoded protein forms the beta subunit of rabconnectin-3 and binds directly with Rab3A GDP/GTP exchange protein and indirectly with Rab3A GDP/GTP activating protein; these proteins are regulators of Rab3 small G protein family members involved in control of the calcium-dependant exocytosis of neurotransmitters. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

WDR7 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 18-56685981-G-A is Benign according to our data. Variant chr18-56685981-G-A is described in ClinVar as [Benign]. Clinvar id is 777896.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.22 with no splicing effect.

BS2

High AC in GnomAd4 at 629 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR7	NM_015285.3 linkuse as main transcript	c.546G>A	p.Val182=	synonymous_variant	6/28	ENST00000254442.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR7	ENST00000254442.8 linkuse as main transcript	c.546G>A	p.Val182=	synonymous_variant	6/28	1	NM_015285.3	P4	Q9Y4E6-1
WDR7	ENST00000357574.7 linkuse as main transcript	c.546G>A	p.Val182=	synonymous_variant	6/27	5		A1	Q9Y4E6-2
WDR7	ENST00000589935.1 linkuse as main transcript	c.-1+34405G>A		intron_variant		4

Frequencies

GnomAD3 genomes

AF:

0.00414

AC:

629

AN:

152032

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.0294

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.000851

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00676

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00396

AC:

950

AN:

240152

Hom.:

AF XY:

0.00402

AC XY:

524

AN XY:

130496

show subpopulations

Gnomad AFR exome

AF:

0.00102

Gnomad AMR exome

AF:

0.000463

Gnomad ASJ exome

AF:

0.0237

Gnomad EAS exome

AF:

0.0000586

Gnomad SAS exome

AF:

0.000443

Gnomad FIN exome

AF:

0.000983

Gnomad NFE exome

AF:

0.00558

Gnomad OTH exome

AF:

0.00573

GnomAD4 exome

AF:

0.00674

AC:

9767

AN:

1449980

Hom.:

Cov.:

AF XY:

0.00649

AC XY:

4682

AN XY:

721560

show subpopulations

Gnomad4 AFR exome

AF:

0.00145

Gnomad4 AMR exome

AF:

0.000512

Gnomad4 ASJ exome

AF:

0.0253

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000640

Gnomad4 FIN exome

AF:

0.00101

Gnomad4 NFE exome

AF:

0.00748

Gnomad4 OTH exome

AF:

0.00997

GnomAD4 genome

AF:

0.00413

AC:

629

AN:

152150

Hom.:

Cov.:

AF XY:

0.00358

AC XY:

266

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.00104

Gnomad4 AMR

AF:

0.000589

Gnomad4 ASJ

AF:

0.0294

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.000851

Gnomad4 NFE

AF:

0.00676

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00666

Hom.:

Bravo

AF:

0.00408

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 24, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

3.6

DANN

Benign

0.43

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