5-140668251-A-C

Position:

• chr5-140668251-A-C

Variant summary

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

The NM_017706.5(WDR55):​c.209A>C​(p.Gln70Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: WDR55 NM_017706.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.37

Genes affected

WDR55 (HGNC:25971): (WD repeat domain 55) Predicted to be involved in rRNA processing. Located in nucleolus and nucleoplasm. [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
WDR55	NM_017706.5	c.209A>C	p.Gln70Pro	missense_variant	2/7	ENST00000358337.10	NP_060176.3
WDR55	XM_005268469.4	c.209A>C	p.Gln70Pro	missense_variant	2/8		XP_005268526.1
WDR55	XM_017009600.3	c.-275A>C		5_prime_UTR_variant	3/8		XP_016865089.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR55	ENST00000358337.10	c.209A>C	p.Gln70Pro	missense_variant	2/7	1	NM_017706.5	ENSP00000351100.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

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

Dec 14, 2021

The c.209A>C (p.Q70P) alteration is located in exon 2 (coding exon 2) of the WDR55 gene. This alteration results from a A to C substitution at nucleotide position 209, causing the glutamine (Q) at amino acid position 70 to be replaced by a proline (P). 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	0.22
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	23
DANN	Benign	0.92
DEOGEN2	Benign	0.051	T
Eigen	Benign	-0.13
Eigen_PC	Benign	0.038
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-1.1	N
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.17
Sift	Benign	0.23	T
Sift4G	Benign	0.34	T
Polyphen		0.054	B
Vest4		0.29
MutPred		0.31		Gain of loop (P = 0.1069);
MVP		0.36
MPC		0.35
ClinPred		0.46	T
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.25
gMVP		0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.24		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.24		Position offset: 3

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: chr5-140047836;