3-167522427-C-A

Variant names:

• chr3-167522427-C-A
• NM_001366157.1:c.2662G>T

Variant summary

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

The NM_001366157.1(WDR49):​c.2662G>T​(p.Val888Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,164 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: WDR49 NM_001366157.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0940

Genes affected

WDR49 (HGNC:26587): (WD repeat domain 49) This gene encodes a member of the WD repeat protein family with nine WD repeats. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2017]

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=0.06562981).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR49	NM_001366157.1	c.2662G>T	p.Val888Leu	missense_variant	Exon 16 of 19	ENST00000682715.1	NP_001353086.1
WDR49	NM_001348951.2	c.2629G>T	p.Val877Leu	missense_variant	Exon 16 of 19		NP_001335880.1
WDR49	NM_001348952.2	c.2629G>T	p.Val877Leu	missense_variant	Exon 16 of 19		NP_001335881.1
WDR49	NM_001366158.1	c.1606G>T	p.Val536Leu	missense_variant	Exon 13 of 16		NP_001353087.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR49	ENST00000682715.1	c.2662G>T	p.Val888Leu	missense_variant	Exon 16 of 19		NM_001366157.1	ENSP00000507497.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459164 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725860

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	3.6
DANN	Benign	0.65
DEOGEN2	Benign	0.0011	T;.
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.48	T;T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.066	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.55	N;.
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.65	N;.
REVEL	Benign	0.0070
Sift	Benign	0.33	T;.
Sift4G	Benign	0.27	T;.
Polyphen		0.0030	B;.
Vest4		0.12
MutPred		0.27		Gain of loop (P = 0.1069);.;
MVP		0.20
MPC		0.029
ClinPred		0.030	T
GERP RS		-1.6
Varity_R		0.048
gMVP		0.054

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr3-167240215; COSMIC: COSV57720278;