1-108982671-C-G

Position:

• chr1-108982671-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001142551.2(WDR47):​c.2204G>C​(p.Cys735Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: WDR47 NM_001142551.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.57

Genes affected

WDR47 (HGNC:29141): (WD repeat domain 47) Predicted to be located in cytoplasm and microtubule. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.833

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR47	NM_001142551.2	c.2204G>C	p.Cys735Ser	missense_variant	12/15	ENST00000369962.8	NP_001136023.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR47	ENST00000369962.8	c.2204G>C	p.Cys735Ser	missense_variant	12/15	1	NM_001142551.2	ENSP00000358979.3
WDR47	ENST00000400794.7	c.2228G>C	p.Cys743Ser	missense_variant	12/15	1		ENSP00000383599.3
WDR47	ENST00000369965.8	c.2207G>C	p.Cys736Ser	missense_variant	12/15	1		ENSP00000358982.4
WDR47	ENST00000361054.7	c.2120G>C	p.Cys707Ser	missense_variant	11/14	5		ENSP00000354339.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 27, 2022

The c.2228G>C (p.C743S) alteration is located in exon 12 (coding exon 11) of the WDR47 gene. This alteration results from a G to C substitution at nucleotide position 2228, causing the cysteine (C) at amino acid position 743 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.26
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	.;T;.;.;T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D;D;D;D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.83	D;D;D;D;D
MetaSVM	Uncertain	-0.26	T
MutationAssessor	Benign	2.0	.;M;.;.;.
PrimateAI	Pathogenic	0.91	D
PROVEAN	Pathogenic	-7.0	D;D;D;D;.
REVEL	Pathogenic	0.76
Sift	Benign	0.036	D;T;T;T;.
Sift4G	Benign	0.14	T;T;T;T;T
Polyphen		1.0, 0.74, 0.55	.;D;P;P;.
Vest4		0.79
MutPred		0.57		.;Gain of disorder (P = 0.0083);.;.;.;
MVP		0.34
MPC		2.2
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.64
gMVP		0.75

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: chr1-109525293;