2-223930021-G-T

Variant names:

• chr2-223930021-G-T
• rs717610
• NM_020830.5:c.138-12011C>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020830.5(WDFY1):​c.138-12011C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.841 in 152,160 control chromosomes in the GnomAD database, including 54,557 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 0.84 (54557 hom., cov: 32)
• Consequence: WDFY1 NM_020830.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.104

Genes affected

WDFY1 (HGNC:20451): (WD repeat and FYVE domain containing 1) The protein encoded by this gene is a phosphatidylinositol 3-phosphate binding protein, which contains a FYVE zinc finger domain and multiple WD-40 repeat domains. When exogenously expressed, it localizes to early endosomes. Mutagenesis analysis demonstrates that this endosomal localization is mediated by the FYVE domain. [provided by RefSeq, Jan 2015]

ENSG00000286239 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.921 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDFY1	NM_020830.5	c.138-12011C>A		intron_variant	Intron 1 of 11	ENST00000233055.9	NP_065881.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDFY1	ENST00000233055.9	c.138-12011C>A		intron_variant	Intron 1 of 11	1	NM_020830.5	ENSP00000233055.4
ENSG00000286239	ENST00000650969.1	n.138-12011C>A		intron_variant	Intron 1 of 16			ENSP00000498456.1
WDFY1	ENST00000429915.1	c.138-12011C>A		intron_variant	Intron 1 of 5	3		ENSP00000395416.1
WDFY1	ENST00000483061.1	n.189-12011C>A		intron_variant	Intron 1 of 4	2

Frequencies

GnomAD3 genomes AF: 0.841 AC: 127900 AN: 152042 Hom.: 54531 Cov.: 32

Gnomad AFR AF: 0.724

Gnomad AMI AF: 0.974

Gnomad AMR AF: 0.844

Gnomad ASJ AF: 0.875

Gnomad EAS AF: 0.543

Gnomad SAS AF: 0.866

Gnomad FIN AF: 0.853

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.927

Gnomad OTH AF: 0.840

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

GnomAD4 genome AF: 0.841 AC: 127978 AN: 152160 Hom.: 54557 Cov.: 32 AF XY: 0.835 AC XY: 62137 AN XY: 74398

Gnomad4 AFR AF: 0.724

Gnomad4 AMR AF: 0.844

Gnomad4 ASJ AF: 0.875

Gnomad4 EAS AF: 0.542

Gnomad4 SAS AF: 0.867

Gnomad4 FIN AF: 0.853

Gnomad4 NFE AF: 0.927

Gnomad4 OTH AF: 0.834

Alfa AF: 0.871 Hom.: 3332

Bravo AF: 0.833

Asia WGS AF: 0.692 AC: 2411 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.6
DANN	Benign	0.40

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

Other links and lift over

dbSNP: rs717610; hg19: chr2-224794738;