1-241687501-A-G

Position:

• chr1-241687501-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000437684.7(WDR64):​c.880A>G​(p.Arg294Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: WDR64 ENST00000437684.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.06

Genes affected

WDR64 (HGNC:26570): (WD repeat domain 64)

LOC124904603 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30457693).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR64	NM_001367482.1	c.880A>G	p.Arg294Gly	missense_variant	8/28	ENST00000437684.7	NP_001354411.1
LOC124904603	XR_007067055.1	n.190-10001T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR64	ENST00000437684.7	c.880A>G	p.Arg294Gly	missense_variant	8/28	1	NM_001367482.1	ENSP00000402446	P1
WDR64	ENST00000366552.6	c.850A>G	p.Arg284Gly	missense_variant	7/27	5		ENSP00000355510
WDR64	ENST00000414635.5	c.163A>G	p.Arg55Gly	missense_variant	2/17	5		ENSP00000406656
WDR64	ENST00000425826.3	c.880A>G	p.Arg294Gly	missense_variant, NMD_transcript_variant	8/29	2		ENSP00000406342

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461652 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727146

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: 0.00

Gnomad4 OTH exome AF: 0.0000166

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

Apr 25, 2022

The c.850A>G (p.R284G) alteration is located in exon 7 (coding exon 7) of the WDR64 gene. This alteration results from a A to G substitution at nucleotide position 850, causing the arginine (R) at amino acid position 284 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	Uncertain	0.34
BayesDel_addAF	Uncertain	0.020	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.079	T;.;.
Eigen	Benign	0.075
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.84	T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.30	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.7	L;.;.
MutationTaster	Benign	0.53	D;N
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-4.1	D;D;N
REVEL	Benign	0.16
Sift	Uncertain	0.0060	D;D;T
Sift4G	Uncertain	0.010	D;D;D
Vest4		0.75
MutPred		0.50		Loss of MoRF binding (P = 0.0268);.;.;
MVP		0.14
MPC		0.19
ClinPred		0.97	D
GERP RS		5.5
Varity_R		0.37
gMVP		0.62

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: chr1-241850803;