18-56686894-T-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_015285.3(WDR7):​c.637T>A​(p.Tyr213Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,457,836 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

WDR7
NM_015285.3 missense

Scores

2
5
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.21
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAdExome4 at 20 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
WDR7NM_015285.3 linkuse as main transcriptc.637T>A p.Tyr213Asn missense_variant 7/28 ENST00000254442.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
WDR7ENST00000254442.8 linkuse as main transcriptc.637T>A p.Tyr213Asn missense_variant 7/281 NM_015285.3 P4Q9Y4E6-1
WDR7ENST00000357574.7 linkuse as main transcriptc.637T>A p.Tyr213Asn missense_variant 7/275 A1Q9Y4E6-2
WDR7ENST00000589935.1 linkuse as main transcriptc.-1+35318T>A intron_variant 4

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.0000137
AC:
20
AN:
1457836
Hom.:
0
Cov.:
33
AF XY:
0.0000179
AC XY:
13
AN XY:
725524
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000162
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsFeb 22, 2023The c.637T>A (p.Y213N) alteration is located in exon 7 (coding exon 6) of the WDR7 gene. This alteration results from a T to A substitution at nucleotide position 637, causing the tyrosine (Y) at amino acid position 213 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.23
BayesDel_addAF
Pathogenic
0.17
D
BayesDel_noAF
Uncertain
0.0
CADD
Benign
23
DANN
Benign
0.89
DEOGEN2
Benign
0.032
.;T
Eigen
Benign
-0.046
Eigen_PC
Benign
0.091
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.97
D;D
M_CAP
Benign
0.024
T
MetaRNN
Uncertain
0.43
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.1
M;M
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Pathogenic
0.80
T
PROVEAN
Benign
0.49
N;N
REVEL
Benign
0.23
Sift
Benign
0.34
T;T
Sift4G
Benign
0.50
T;T
Polyphen
0.75
P;B
Vest4
0.75
MutPred
0.58
Gain of disorder (P = 0.0172);Gain of disorder (P = 0.0172);
MVP
0.20
MPC
0.66
ClinPred
0.58
D
GERP RS
4.9
Varity_R
0.16
gMVP
0.35

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs1235594512; hg19: chr18-54354125; API