chr19-37885389-T-C

Position:

• chr19-37885389-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001291088.2(WDR87):​c.8282A>G​(p.Glu2761Gly) 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. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: WDR87 NM_001291088.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.150

Genes affected

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

LOC105372395 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.051732004).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR87	NM_001291088.2	c.8282A>G	p.Glu2761Gly	missense_variant	6/6	ENST00000447313.7
LOC105372395	XR_935962.3	n.621+890T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR87	ENST00000447313.7	c.8282A>G	p.Glu2761Gly	missense_variant	6/6	2	NM_001291088.2	A2
WDR87	ENST00000303868.5	c.8165A>G	p.Glu2722Gly	missense_variant	6/6	2		P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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

Feb 15, 2023

The c.8165A>G (p.E2722G) alteration is located in exon 6 (coding exon 5) of the WDR87 gene. This alteration results from a A to G substitution at nucleotide position 8165, causing the glutamic acid (E) at amino acid position 2722 to be replaced by a glycine (G). 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	0.12
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	17
DANN	Benign	0.55
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.42	T;.
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.052	T;T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-2.4	N;N
REVEL	Benign	0.015
Sift	Benign	0.031	D;D
Sift4G	Uncertain	0.0080	D;D
Polyphen		0.0030	B;.
Vest4		0.053
MutPred		0.23		Loss of ubiquitination at K2759 (P = 0.0547);.;
MVP		0.13
ClinPred		0.036	T
GERP RS		2.4
gMVP		0.057

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: rs374652986; hg19: chr19-38376029;