Variant chr2-24037858-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_025203.3(WDCP):c.1637A>G(p.Lys546Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000234 in 1,614,108 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00024 ( 1 hom. )

Consequence

WDCP
NM_025203.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.652

Variant links:

Genes affected

WDCP (HGNC:26157): (WD repeat and coiled coil containing) Enables kinase binding activity. Involved in protein complex oligomerization. [provided by Alliance of Genome Resources, Apr 2022]

WDCP links:

FKBP1B (HGNC:):

FKBP1B links:

MFSD2B (HGNC:37207): (MFSD2 lysolipid transporter B, sphingolipid) Enables sphingolipid transporter activity. Involved in lipid transport. Is integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

MFSD2B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.005484253).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
WDCP	NM_025203.3 linkuse as main transcript	c.1637A>G	p.Lys546Arg	missense_variant	2/4	ENST00000295148.9
WDCP	NM_001142319.2 linkuse as main transcript	c.1637A>G	p.Lys546Arg	missense_variant	2/3
FKBP1B	XM_017003594.2 linkuse as main transcript	c.-51+4601T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDCP	ENST00000295148.9 linkuse as main transcript	c.1637A>G	p.Lys546Arg	missense_variant	2/4	2	NM_025203.3	P1	Q9H6R7-1
WDCP	ENST00000406895.3 linkuse as main transcript	c.1637A>G	p.Lys546Arg	missense_variant	2/3	1			Q9H6R7-2
MFSD2B	ENST00000453731.1 linkuse as main transcript	c.*75+4601T>C		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000217

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00720

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000398

AC:

100

AN:

251392

Hom.:

AF XY:

0.000368

AC XY:

AN XY:

135882

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00853

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000967

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000235

AC:

344

AN:

1461870

Hom.:

Cov.:

AF XY:

0.000231

AC XY:

168

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00861

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000710

Gnomad4 OTH exome

AF:

0.000646

GnomAD4 genome

AF:

0.000217

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00720

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00143

Alfa

AF:

0.000712

Hom.:

Bravo

AF:

0.000257

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000305

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000237

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 submitter

clinical testing

Ambry Genetics

Nov 27, 2023

The c.1637A>G (p.K546R) alteration is located in exon 2 (coding exon 1) of the WDCP gene. This alteration results from a A to G substitution at nucleotide position 1637, causing the lysine (K) at amino acid position 546 to be replaced by an arginine (R). 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

Benign

0.077

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.69

CADD

Benign

1.8

DANN

Benign

0.91

DEOGEN2

Benign

0.0031

T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.40

T;T

M_CAP

Benign

0.0092

MetaRNN

Benign

0.0055

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N

PROVEAN

Benign

-0.80

N;N

REVEL

Benign

0.030

Sift

Benign

0.24

T;T

Sift4G

Benign

0.47

T;T

Polyphen

0.0040

B;B

Vest4

0.056

MVP

0.26

MPC

0.090

ClinPred

0.0073

GERP RS

0.13

Varity_R

0.024

gMVP

0.086

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over