rs74518295

Variant names:

• chr19-36101667-C-G
• NM_001083961.2:c.2975C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-36101667-C-G
• chr19-36101667-C-T

Variant summary

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

The NM_001083961.2(WDR62):​c.2975C>G​(p.Ser992Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,398,124 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 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. S992L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: WDR62 NM_001083961.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0800

Genes affected

WDR62 (HGNC:24502): (WD repeat domain 62) This gene is proposed to play a role in cerebral cortical development. Mutations in this gene have been associated with microencephaly, cortical malformations, and cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR62	NM_001083961.2	c.2975C>G	p.Ser992Trp	missense_variant	Exon 25 of 32	ENST00000401500.7	NP_001077430.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR62	ENST00000401500.7	c.2975C>G	p.Ser992Trp	missense_variant	Exon 25 of 32	1	NM_001083961.2	ENSP00000384792.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1398124 Hom.: 0 Cov.: 32 AF XY: 0.00000290 AC XY: 2 AN XY: 689616

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: 9.27e-7

Gnomad4 OTH exome AF: 0.0000172

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.024	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	.;T
Eigen	Benign	-0.0015
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.85	D;D
M_CAP	Benign	0.069	D
MetaRNN	Uncertain	0.44	T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.1	M;M
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-2.4	N;N
REVEL	Benign	0.21
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0060	D;D
Polyphen		0.99	D;D
Vest4		0.50
MutPred		0.23		Loss of phosphorylation at S992 (P = 0.0023);Loss of phosphorylation at S992 (P = 0.0023);
MVP		0.58
MPC		0.96
ClinPred		0.77	D
GERP RS		2.7
Varity_R		0.14
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-36592569;