rs17763463

Variant names:

• chr2-24033201-T-C
• rs17763463
• NM_025203.3:c.1819-255A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025203.3(WDCP):​c.1819-255A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0908 in 568,198 control chromosomes in the GnomAD database, including 2,704 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 0.081 (570 hom., cov: 32)
  • Exomes 𝑓: 0.095 (2134 hom.)
• Consequence: WDCP NM_025203.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.398
• Publications: 3 publications found

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]

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]

FKBP1B (HGNC:3712): (FKBP prolyl isomerase 1B) The protein encoded by this gene is a member of the immunophilin protein family, which play a role in immunoregulation and basic cellular processes involving protein folding and trafficking. This encoded protein is a cis-trans prolyl isomerase that binds the immunosuppressants FK506 and rapamycin. It is highly similar to the FK506-binding protein 1A. Its physiological role is thought to be in excitation-contraction coupling in cardiac muscle. There are two alternatively spliced transcript variants of this gene encoding different isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025203.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDCP	NM_025203.3	MANE Select	c.1819-255A>G		intron	N/A	NP_079479.1	Q9H6R7-1
	WDCP	NM_001142319.2		c.1819-2039A>G		intron	N/A	NP_001135791.1	Q9H6R7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDCP	ENST00000295148.9	TSL:2 MANE Select	c.1819-255A>G		intron	N/A	ENSP00000295148.4	Q9H6R7-1
	WDCP	ENST00000406895.3	TSL:1	c.1819-2039A>G		intron	N/A	ENSP00000385816.3	Q9H6R7-2
	MFSD2B	ENST00000453731.1	TSL:3	n.*19T>C		non_coding_transcript_exon	Exon 2 of 5	ENSP00000390490.1	H7BZN4

Frequencies

GnomAD3 genomes AF: 0.0806 AC: 12254 AN: 152062 Hom.: 572 Cov.: 32

Gnomad AFR AF: 0.0552

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.0778

Gnomad ASJ AF: 0.0772

Gnomad EAS AF: 0.0148

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.0620

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0982

Gnomad OTH AF: 0.0894

GnomAD2 exomes AF: 0.0851 AC: 12444 AN: 146236 AF XY: 0.0919

Gnomad AFR exome AF: 0.0539

Gnomad AMR exome AF: 0.0477

Gnomad ASJ exome AF: 0.0770

Gnomad EAS exome AF: 0.0121

Gnomad FIN exome AF: 0.0666

Gnomad NFE exome AF: 0.100

Gnomad OTH exome AF: 0.103

GnomAD4 exome AF: 0.0946 AC: 39346 AN: 416018 Hom.: 2134 Cov.: 0 AF XY: 0.100 AC XY: 22938 AN XY: 229378

African (AFR) AF: 0.0519 AC: 637 AN: 12280

American (AMR) AF: 0.0500 AC: 1508 AN: 30160

Ashkenazi Jewish (ASJ) AF: 0.0790 AC: 1185 AN: 14998

East Asian (EAS) AF: 0.0228 AC: 402 AN: 17658

South Asian (SAS) AF: 0.147 AC: 8913 AN: 60552

European-Finnish (FIN) AF: 0.0675 AC: 2197 AN: 32560

Middle Eastern (MID) AF: 0.128 AC: 427 AN: 3348

European-Non Finnish (NFE) AF: 0.0995 AC: 22206 AN: 223130

Other (OTH) AF: 0.0877 AC: 1871 AN: 21332

GnomAD4 genome AF: 0.0806 AC: 12259 AN: 152180 Hom.: 570 Cov.: 32 AF XY: 0.0801 AC XY: 5957 AN XY: 74404

African (AFR) AF: 0.0552 AC: 2292 AN: 41530

American (AMR) AF: 0.0777 AC: 1187 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0772 AC: 268 AN: 3470

East Asian (EAS) AF: 0.0151 AC: 78 AN: 5178

South Asian (SAS) AF: 0.148 AC: 714 AN: 4826

European-Finnish (FIN) AF: 0.0620 AC: 656 AN: 10588

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0983 AC: 6682 AN: 67994

Other (OTH) AF: 0.0889 AC: 188 AN: 2114

Alfa AF: 0.0938 Hom.: 1243

Bravo AF: 0.0785

Asia WGS AF: 0.0810 AC: 281 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.6
DANN	Benign	0.73
PhyloP100		-0.40
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17763463; hg19: chr2-24256071;