rs193921101

Variant names:

• chr3-167527959-G-C
• NM_001366157.1:c.2465C>G

Your query was ambiguous. Multiple possible variants found:

• chr3-167527959-G-C
• chr3-167527959-G-T

Variant summary

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

The NM_001366157.1(WDR49):​c.2465C>G​(p.Ser822*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,136 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: WDR49 NM_001366157.1 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.83

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 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
WDR49	NM_001366157.1	c.2465C>G	p.Ser822*	stop_gained	Exon 15 of 19	ENST00000682715.1	NP_001353086.1
WDR49	NM_001348951.2	c.2432C>G	p.Ser811*	stop_gained	Exon 15 of 19		NP_001335880.1
WDR49	NM_001348952.2	c.2432C>G	p.Ser811*	stop_gained	Exon 15 of 19		NP_001335881.1
WDR49	NM_001366158.1	c.1409C>G	p.Ser470*	stop_gained	Exon 12 of 16		NP_001353087.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR49	ENST00000682715.1	c.2465C>G	p.Ser822*	stop_gained	Exon 15 of 19		NM_001366157.1	ENSP00000507497.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461136 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726874

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
BayesDel_addAF	Pathogenic	0.55	D
BayesDel_noAF	Pathogenic	0.55
CADD	Pathogenic	35
DANN	Uncertain	0.99
Eigen	Pathogenic	0.70
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.86	D
Vest4		0.24
GERP RS		5.5

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-167245747;