chr19-37885005-G-A

Position:

• chr19-37885005-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001291088.2(WDR87):​c.8666C>T​(p.Ala2889Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000159 in 1,254,278 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: WDR87 NM_001291088.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.06

Genes affected

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

LOC105372395 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41321415).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR87	NM_001291088.2	c.8666C>T	p.Ala2889Val	missense_variant	6/6	ENST00000447313.7	NP_001278017.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR87	ENST00000447313.7	c.8666C>T	p.Ala2889Val	missense_variant	6/6	2	NM_001291088.2	ENSP00000405012.2
WDR87	ENST00000303868.5	c.8549C>T	p.Ala2850Val	missense_variant	6/6	2		ENSP00000368025.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000159 AC: 2 AN: 1254278 Hom.: 0 Cov.: 30 AF XY: 0.00000331 AC XY: 2 AN XY: 604826

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: 0.00000198

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

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

Apr 17, 2024

The c.8549C>T (p.A2850V) 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 8549, causing the alanine (A) at amino acid position 2850 to be replaced by a valine (V). 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	0.56
BayesDel_addAF	Benign	-0.093	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	24
DANN	Benign	0.94
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.61	T;.
M_CAP	Benign	0.055	D
MetaRNN	Benign	0.41	T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-2.1	N;N
REVEL	Benign	0.15
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.53
MutPred		0.27		Gain of methylation at K2891 (P = 0.0765);.;
MVP		0.11
ClinPred		0.71	D
GERP RS		4.6
gMVP		0.25

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: rs1486266740; hg19: chr19-38375645;