13-51584755-C-A

Variant names:

• chr13-51584755-C-A
• rs1253889825
• NM_052950.4:c.68C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_052950.4(WDFY2):​c.68C>A​(p.Ser23Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S23F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: WDFY2 NM_052950.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.64
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39121547).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052950.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDFY2	NM_052950.4	MANE Select	c.68C>A	p.Ser23Tyr	missense	Exon 1 of 12	NP_443182.1	Q96P53

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDFY2	ENST00000298125.7	TSL:1 MANE Select	c.68C>A	p.Ser23Tyr	missense	Exon 1 of 12	ENSP00000298125.4	Q96P53
	WDFY2	ENST00000923033.1		c.68C>A	p.Ser23Tyr	missense	Exon 1 of 12	ENSP00000593092.1
	WDFY2	ENST00000876143.1		c.68C>A	p.Ser23Tyr	missense	Exon 1 of 12	ENSP00000546202.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	0.0079	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	21
DANN	Benign	0.89
DEOGEN2	Benign	0.0099	T
Eigen	Benign	0.0072
Eigen_PC	Benign	0.18
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.063	D
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.4	L
PhyloP100		2.6
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.16
Sift	Benign	1.0	T
Sift4G	Benign	0.19	T
Polyphen		0.14	B
Vest4		0.54
MutPred		0.63		Loss of disorder (P = 0.0084)
MVP		0.70
MPC		0.50
ClinPred		0.34	T
GERP RS		5.0
PromoterAI		0.049	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.27
gMVP		0.49
Mutation Taster		=60/40	polymorphism

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

Other links and lift over

dbSNP: rs1253889825; hg19: chr13-52158891;