19-37884949-C-A

Variant names:

• chr19-37884949-C-A
• rs758509402
• NM_001291088.2:c.8722G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001291088.2(WDR87):​c.8722G>T​(p.Val2908Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000859 in 1,164,074 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V2908I) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 8.6e-7 (0 hom.)
• Consequence: WDR87 NM_001291088.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.983
• Publications: 0 publications found

Genes affected

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

WDR87 Gene-Disease associations (from GenCC):

• cataract

  Inheritance: AR Classification: LIMITED Submitted by: G2P

LOC105372395 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.114681035).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001291088.2. 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
	WDR87	NM_001291088.2	MANE Select	c.8722G>T	p.Val2908Phe	missense	Exon 6 of 6	NP_001278017.1	A0AA75ISB7
	WDR87	NM_031951.5		c.8605G>T	p.Val2869Phe	missense	Exon 6 of 6	NP_114157.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR87	ENST00000447313.7	TSL:2 MANE Select	c.8722G>T	p.Val2908Phe	missense	Exon 6 of 6	ENSP00000405012.2	A0AA75ISB7
	WDR87	ENST00000303868.5	TSL:2	c.8605G>T	p.Val2869Phe	missense	Exon 6 of 6	ENSP00000368025.3	Q6ZQQ6-1
	ENSG00000291089	ENST00000801875.1		n.*108C>A		downstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 8.59e-7 AC: 1 AN: 1164074 Hom.: 0 Cov.: 30 AF XY: 0.00000181 AC XY: 1 AN XY: 553844

African (AFR) AF: 0.00 AC: 0 AN: 24504

American (AMR) AF: 0.00 AC: 0 AN: 12630

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15638

East Asian (EAS) AF: 0.00 AC: 0 AN: 29480

South Asian (SAS) AF: 0.00 AC: 0 AN: 30500

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40640

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4766

European-Non Finnish (NFE) AF: 0.00000104 AC: 1 AN: 958536

Other (OTH) AF: 0.00 AC: 0 AN: 47380

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	1.8
DANN	Benign	0.43
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.98
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.89	N
REVEL	Benign	0.18
Sift	Benign	0.082	T
Sift4G	Uncertain	0.044	D
Polyphen		0.95	P
Vest4		0.080
MutPred		0.076		Gain of helix (P = 0.0854)
MVP		0.030
ClinPred		0.15	T
GERP RS		-5.8
gMVP		0.13
Mutation Taster		=100/0	polymorphism

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: rs758509402; hg19: chr19-38375589;