rs746369214

Variant names:

• chr2-63122037-G-A
• rs746369214
• NM_015910.7:c.2210C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-63122037-G-A
• chr2-63122037-G-T

Variant summary

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

The NM_015910.7(WDPCP):​c.2210C>T​(p.Ser737Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,694 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: WDPCP NM_015910.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.90

Genes affected

WDPCP (HGNC:28027): (WD repeat containing planar cell polarity effector) This gene encodes a cytoplasmic WD40 repeat protein. A similar gene in frogs encodes a planar cell polarity protein that plays a critical role in collective cell movement and ciliogenesis by mediating septin localization. Mutations in this gene are associated with Bardet-Biedl syndrome 15 and may also play a role in Meckel-Gruber syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

ENSG00000286480 (HGNC:):

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=0.22138849).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDPCP	NM_015910.7	c.2210C>T	p.Ser737Phe	missense_variant	Exon 18 of 18	ENST00000272321.12	NP_056994.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDPCP	ENST00000272321.12	c.2210C>T	p.Ser737Phe	missense_variant	Exon 18 of 18	1	NM_015910.7	ENSP00000272321.7

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460694 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726642

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000828 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	0.0078	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0063	T;.;.;.
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.017
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.72	T;.;T;T
M_CAP	Benign	0.055	D
MetaRNN	Benign	0.22	T;T;T;T
MetaSVM	Benign	-0.68	T
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.9	N;N;N;N
REVEL	Benign	0.14
Sift	Pathogenic	0.0	D;D;D;D
Sift4G	Uncertain	0.0090	D;D;D;D
Polyphen		0.0030	B;.;.;B
Vest4		0.13
MutPred		0.36		Loss of disorder (P = 0.0071);.;.;.;
MVP		0.80
MPC		0.31
ClinPred		0.99	D
GERP RS		4.4
Varity_R		0.27
gMVP		0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs746369214; hg19: chr2-63349172; COSMIC: COSV55421781; COSMIC: COSV55421781;