1-108971521-T-C

Position:

• chr1-108971521-T-C

Variant summary

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

The NM_001142551.2(WDR47):​c.2669A>G​(p.Lys890Arg) 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.2669A>G	p.Lys890Arg	missense_variant	15/15	ENST00000369962.8	NP_001136023.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR47	ENST00000369962.8	c.2669A>G	p.Lys890Arg	missense_variant	15/15	1	NM_001142551.2	ENSP00000358979	A1
WDR47	ENST00000400794.7	c.2693A>G	p.Lys898Arg	missense_variant	15/15	1		ENSP00000383599
WDR47	ENST00000369965.8	c.2672A>G	p.Lys891Arg	missense_variant	15/15	1		ENSP00000358982	P5
WDR47	ENST00000361054.7	c.2585A>G	p.Lys862Arg	missense_variant	14/14	5		ENSP00000354339

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Aug 02, 2022

The c.2693A>G (p.K898R) alteration is located in exon 15 (coding exon 14) of the WDR47 gene. This alteration results from a A to G substitution at nucleotide position 2693, causing the lysine (K) at amino acid position 898 to be replaced by an arginine (R). 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	0.88
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	.;T;.;.;T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D;D;D;D;D
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.49	T;T;T;T;T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	1.9	.;L;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-2.5	N;N;D;N;.
REVEL	Uncertain	0.34
Sift	Pathogenic	0.0	D;D;D;D;.
Sift4G	Uncertain	0.010	D;D;D;D;D
Polyphen		1.0, 0.99, 0.98	.;D;D;D;.
Vest4		0.57
MutPred		0.48		.;Loss of ubiquitination at K890 (P = 0.021);.;.;.;
MVP		0.44
MPC		1.8
ClinPred		0.94	D
GERP RS		6.0
Varity_R		0.49
gMVP		0.30

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: chr1-109514143;