2-24037829-G-C

Position:

• chr2-24037829-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_025203.3(WDCP):​c.1666C>G​(p.Gln556Glu) 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. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: WDCP NM_025203.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.262

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]

FKBP1B (HGNC:):

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]

ACMG classification

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=0.04059273).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDCP	NM_025203.3	c.1666C>G	p.Gln556Glu	missense_variant	2/4	ENST00000295148.9
WDCP	NM_001142319.2	c.1666C>G	p.Gln556Glu	missense_variant	2/3
FKBP1B	XM_017003594.2	c.-51+4572G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDCP	ENST00000295148.9	c.1666C>G	p.Gln556Glu	missense_variant	2/4	2	NM_025203.3	P1
WDCP	ENST00000406895.3	c.1666C>G	p.Gln556Glu	missense_variant	2/3	1
MFSD2B	ENST00000453731.1	c.*75+4572G>C		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 09, 2021

The c.1666C>G (p.Q556E) alteration is located in exon 2 (coding exon 1) of the WDCP gene. This alteration results from a C to G substitution at nucleotide position 1666, causing the glutamine (Q) at amino acid position 556 to be replaced by a glutamic acid (E). 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	0.078
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.41
DANN	Benign	0.43
DEOGEN2	Benign	0.0079	T;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.36	T;T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.041	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.067
Sift	Benign	0.45	T;T
Sift4G	Benign	0.33	T;T
Polyphen		0.0010	B;B
Vest4		0.061
MutPred		0.083		Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);
MVP		0.14
MPC		0.11
ClinPred		0.20	T
GERP RS		2.9
Varity_R		0.044
gMVP		0.22

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-24260699;