2-223876683-G-C

Position:

• chr2-223876683-G-C

Variant summary

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

The NM_020830.5(WDFY1):​c.*1988C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0526 in 152,190 control chromosomes in the GnomAD database, including 451 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 0.053 (451 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: WDFY1 NM_020830.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.125

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDFY1	NM_020830.5	c.*1988C>G		3_prime_UTR_variant	12/12	ENST00000233055.9	NP_065881.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDFY1	ENST00000233055.9	c.*1988C>G		3_prime_UTR_variant	12/12	1	NM_020830.5	ENSP00000233055	P1
WDFY1	ENST00000462702.1	n.160+1846C>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0526 AC: 7996 AN: 152072 Hom.: 449 Cov.: 32

Gnomad AFR AF: 0.0824

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0911

Gnomad ASJ AF: 0.0274

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.0735

Gnomad FIN AF: 0.0397

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0118

Gnomad OTH AF: 0.0575

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.0526 AC: 8011 AN: 152190 Hom.: 451 Cov.: 32 AF XY: 0.0568 AC XY: 4226 AN XY: 74406

Gnomad4 AFR AF: 0.0824

Gnomad4 AMR AF: 0.0915

Gnomad4 ASJ AF: 0.0274

Gnomad4 EAS AF: 0.270

Gnomad4 SAS AF: 0.0726

Gnomad4 FIN AF: 0.0397

Gnomad4 NFE AF: 0.0118

Gnomad4 OTH AF: 0.0592

Alfa AF: 0.0358 Hom.: 30

Bravo AF: 0.0583

Asia WGS AF: 0.149 AC: 517 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	7.0
DANN	Benign	0.76

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: rs10498155; hg19: chr2-224741400;