chr13-51660643-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_052950.4(WDFY2):​c.185G>A​(p.Ser62Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

WDFY2
NM_052950.4 missense

Scores

4
9
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.94
Variant links:
Genes affected
WDFY2 (HGNC:20482): (WD repeat and FYVE domain containing 2) This gene encodes a protein that contains two WD domains and an FYVE zinc finger region. The function of this gene is unknown. An alternatively spliced transcript variant of this gene may exist. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.803

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
WDFY2NM_052950.4 linkuse as main transcriptc.185G>A p.Ser62Asn missense_variant 2/12 ENST00000298125.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
WDFY2ENST00000298125.7 linkuse as main transcriptc.185G>A p.Ser62Asn missense_variant 2/121 NM_052950.4 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

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 GeneticsJul 06, 2022The c.185G>A (p.S62N) alteration is located in exon 2 (coding exon 2) of the WDFY2 gene. This alteration results from a G to A substitution at nucleotide position 185, causing the serine (S) at amino acid position 62 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
Pathogenic
0.96
BayesDel_addAF
Benign
-0.0082
T
BayesDel_noAF
Benign
-0.25
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.17
T
Eigen
Pathogenic
0.80
Eigen_PC
Pathogenic
0.79
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.93
D
M_CAP
Uncertain
0.094
D
MetaRNN
Pathogenic
0.80
D
MetaSVM
Benign
-0.29
T
MutationAssessor
Uncertain
2.9
M
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.63
T
PROVEAN
Uncertain
-2.6
D
REVEL
Benign
0.25
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.0020
D
Polyphen
0.97
D
Vest4
0.68
MutPred
0.29
Gain of MoRF binding (P = 0.123);
MVP
0.80
MPC
1.1
ClinPred
0.99
D
GERP RS
5.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.66
gMVP
0.33

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-52234779; API