rs2663052

Variant names:

• chr10-48861350-G-A
• rs2663052
• NM_001394531.1:c.6664-5915G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-48861350-G-A
• chr10-48861350-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001394531.1(WDFY4):​c.6664-5915G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 151,902 control chromosomes in the GnomAD database, including 25,147 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.56 (25147 hom., cov: 32)
• Consequence: WDFY4 NM_001394531.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.335
• Publications: 15 publications found

Genes affected

WDFY4 (HGNC:29323): (WDFY family member 4) Predicted to be involved in autophagy. Predicted to act upstream of or within with a positive effect on CD8-positive, alpha-beta T cell activation. Predicted to act upstream of or within antigen processing and presentation and cellular response to virus. Predicted to be located in early endosome and endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

WDFY4 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394531.1. 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
	WDFY4	NM_001394531.1	MANE Select	c.6664-5915G>A		intron	N/A	NP_001381460.1
	WDFY4	NM_020945.2		c.6664-5915G>A		intron	N/A	NP_065996.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDFY4	ENST00000325239.12	TSL:5 MANE Select	c.6664-5915G>A		intron	N/A	ENSP00000320563.5
	WDFY4	ENST00000858472.1		c.6664-5915G>A		intron	N/A	ENSP00000528531.1

Frequencies

GnomAD3 genomes AF: 0.561 AC: 85113 AN: 151784 Hom.: 25114 Cov.: 32

Gnomad AFR AF: 0.748

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.707

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.465

Gnomad OTH AF: 0.576

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.561 AC: 85198 AN: 151902 Hom.: 25147 Cov.: 32 AF XY: 0.560 AC XY: 41603 AN XY: 74252

African (AFR) AF: 0.747 AC: 31002 AN: 41476

American (AMR) AF: 0.486 AC: 7421 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.518 AC: 1797 AN: 3468

East Asian (EAS) AF: 0.708 AC: 3658 AN: 5164

South Asian (SAS) AF: 0.542 AC: 2610 AN: 4814

European-Finnish (FIN) AF: 0.503 AC: 5300 AN: 10542

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.465 AC: 31551 AN: 67870

Other (OTH) AF: 0.572 AC: 1206 AN: 2108

Alfa AF: 0.499 Hom.: 61779

Bravo AF: 0.569

Asia WGS AF: 0.572 AC: 1989 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.6
DANN	Benign	0.34
PhyloP100		0.34
Mutation Taster		=100/0	polymorphism (auto)

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: rs2663052; hg19: chr10-50069395; COSMIC: COSV55429624;