chr2-24038895-A-T

Position:

• chr2-24038895-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_025203.3(WDCP):​c.600T>A​(p.Phe200Leu) 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. 12/19 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: 0.246

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17961597).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDCP	NM_025203.3	c.600T>A	p.Phe200Leu	missense_variant	2/4	ENST00000295148.9
WDCP	NM_001142319.2	c.600T>A	p.Phe200Leu	missense_variant	2/3
FKBP1B	XM_017003594.2	c.-51+5638A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDCP	ENST00000295148.9	c.600T>A	p.Phe200Leu	missense_variant	2/4	2	NM_025203.3	P1
WDCP	ENST00000406895.3	c.600T>A	p.Phe200Leu	missense_variant	2/3	1
MFSD2B	ENST00000453731.1	c.*75+5638A>T		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 02, 2021

The c.600T>A (p.F200L) alteration is located in exon 2 (coding exon 1) of the WDCP gene. This alteration results from a T to A substitution at nucleotide position 600, causing the phenylalanine (F) at amino acid position 200 to be replaced by a leucine (L). 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	Uncertain	0.48
BayesDel_addAF	Benign	-0.077	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	7.2
DANN	Benign	0.97
DEOGEN2	Benign	0.18	T;.
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.51
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.62	T;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	D;D
PROVEAN	Uncertain	-4.3	D;D
REVEL	Benign	0.18
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.20	B;B
Vest4		0.22
MutPred		0.64		Loss of catalytic residue at F200 (P = 0.0563);Loss of catalytic residue at F200 (P = 0.0563);
MVP		0.31
MPC		0.13
ClinPred		0.97	D
GERP RS		-1.3
Varity_R		0.73
gMVP		0.66

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: chr2-24261765;