chr1-108983299-T-C

Position:

• chr1-108983299-T-C

Variant summary

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

The NM_001142551.2(WDR47):​c.2078A>G​(p.Glu693Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 7.67

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR47	NM_001142551.2	c.2078A>G	p.Glu693Gly	missense_variant	11/15	ENST00000369962.8	NP_001136023.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR47	ENST00000369962.8	c.2078A>G	p.Glu693Gly	missense_variant	11/15	1	NM_001142551.2	ENSP00000358979.3
WDR47	ENST00000400794.7	c.2102A>G	p.Glu701Gly	missense_variant	11/15	1		ENSP00000383599.3
WDR47	ENST00000369965.8	c.2081A>G	p.Glu694Gly	missense_variant	11/15	1		ENSP00000358982.4
WDR47	ENST00000361054.7	c.1994A>G	p.Glu665Gly	missense_variant	10/14	5		ENSP00000354339.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

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

Aug 14, 2024

The c.2102A>G (p.E701G) alteration is located in exon 11 (coding exon 10) of the WDR47 gene. This alteration results from a A to G substitution at nucleotide position 2102, causing the glutamic acid (E) at amino acid position 701 to be replaced by a glycine (G). 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	Benign	0.21
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	.;T;.;.;T
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.97	D;D;D;D;D
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.64	D;D;D;D;D
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	0.81	.;L;.;.;.
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-3.0	D;D;D;D;D
REVEL	Uncertain	0.61
Sift	Benign	0.054	T;T;T;T;T
Sift4G	Uncertain	0.033	D;D;D;D;D
Polyphen		0.80, 0.55, 0.34	.;P;P;B;.
Vest4		0.74
MutPred		0.48		.;Loss of stability (P = 0.0506);.;.;.;
MVP		0.44
MPC		1.4
ClinPred		0.94	D
GERP RS		5.5
Varity_R		0.29
gMVP		0.37

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

LitVar

Other links and lift over

dbSNP: rs1431255717; hg19: chr1-109525921;