19-37885344-C-G

Variant names:

• chr19-37885344-C-G
• rs200596982
• NM_001291088.2:c.8327G>C

Variant summary

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

The NM_001291088.2(WDR87):​c.8327G>C​(p.Arg2776Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,430 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R2776Q) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: WDR87 NM_001291088.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.979
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.8327G>C	p.Arg2776Pro	missense	Exon 6 of 6	NP_001278017.1	A0AA75ISB7
	WDR87	NM_031951.5		c.8210G>C	p.Arg2737Pro	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.8327G>C	p.Arg2776Pro	missense	Exon 6 of 6	ENSP00000405012.2	A0AA75ISB7
	WDR87	ENST00000303868.5	TSL:2	c.8210G>C	p.Arg2737Pro	missense	Exon 6 of 6	ENSP00000368025.3	Q6ZQQ6-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399430 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 690218

African (AFR) AF: 0.00 AC: 0 AN: 31598

American (AMR) AF: 0.00 AC: 0 AN: 35702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25178

East Asian (EAS) AF: 0.00 AC: 0 AN: 35738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49298

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078974

Other (OTH) AF: 0.0000172 AC: 1 AN: 58018

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Benign	-0.061	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	23
DANN	Benign	0.93
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.071	D
MetaRNN	Uncertain	0.50	D
MetaSVM	Benign	-0.99	T
PhyloP100		0.98
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.17
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.011	D
Polyphen		1.0	D
Vest4		0.58
MutPred		0.45		Loss of MoRF binding (P = 0.008)
MVP		0.35
ClinPred		0.76	D
GERP RS		2.6
gMVP		0.52
Mutation Taster		=79/21	polymorphism

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

Other links and lift over

dbSNP: rs200596982; hg19: chr19-38375984;