chr19-37885111-G-A

Position:

• chr19-37885111-G-A

Variant summary

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

The NM_001291088.2(WDR87):​c.8560C>T​(p.Pro2854Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000229 in 1,312,414 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P2854L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: WDR87 NM_001291088.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.753

Genes affected

WDR87 (HGNC:29934): (WD repeat domain 87)

LOC105372395 (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=0.07663956).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR87	NM_001291088.2	c.8560C>T	p.Pro2854Ser	missense_variant	6/6	ENST00000447313.7
LOC105372395	XR_935962.3	n.621+612G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR87	ENST00000447313.7	c.8560C>T	p.Pro2854Ser	missense_variant	6/6	2	NM_001291088.2	A2
WDR87	ENST00000303868.5	c.8443C>T	p.Pro2815Ser	missense_variant	6/6	2		P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000229 AC: 3 AN: 1312414 Hom.: 0 Cov.: 32 AF XY: 0.00000313 AC XY: 2 AN XY: 638524

Gnomad4 AFR exome AF: 0.00

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: 0.00000288

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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 15, 2023

The c.8443C>T (p.P2815S) alteration is located in exon 6 (coding exon 5) of the WDR87 gene. This alteration results from a C to T substitution at nucleotide position 8443, causing the proline (P) at amino acid position 2815 to be replaced by a serine (S). 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	0.11
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	12
DANN	Benign	0.28
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.38	T;.
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.077	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-3.4	D;D
REVEL	Benign	0.079
Sift	Benign	0.053	T;T
Sift4G	Uncertain	0.056	T;T
Polyphen		0.0060	B;.
Vest4		0.061
MutPred		0.18		Loss of phosphorylation at T2853 (P = 0.0773);.;
MVP		0.076
ClinPred		0.067	T
GERP RS		0.11
gMVP		0.095

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

Other links and lift over

dbSNP: rs2046131331; hg19: chr19-38375751;