5-37396540-G-T

Position:

• chr5-37396540-G-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_018034.4(WDR70):​c.462G>T​(p.Glu154Asp) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: WDR70 NM_018034.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.312

Genes affected

WDR70 (HGNC:25495): (WD repeat domain 70) Enables enzyme binding activity. Predicted to be involved in regulation of DNA double-strand break processing and regulation of histone H2B conserved C-terminal lysine ubiquitination. Predicted to be active in nucleus and site of double-strand break. [provided by Alliance of Genome Resources, Apr 2022]

WDR70 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03890881).
• BP6: Variant 5-37396540-G-T is Benign according to our data. Variant chr5-37396540-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2611677.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR70	NM_018034.4	c.462G>T	p.Glu154Asp	missense_variant	5/18	ENST00000265107.9	NP_060504.1
WDR70	NM_001345998.2	c.459G>T	p.Glu153Asp	missense_variant	5/18		NP_001332927.1
WDR70	NM_001345999.2	c.396G>T	p.Glu132Asp	missense_variant	4/17		NP_001332928.1
WDR70	XM_047417348.1	c.393G>T	p.Glu131Asp	missense_variant	4/17		XP_047273304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR70	ENST00000265107.9	c.462G>T	p.Glu154Asp	missense_variant	5/18	1	NM_018034.4	ENSP00000265107.4
WDR70	ENST00000504564.1	c.462G>T	p.Glu154Asp	missense_variant	5/12	1		ENSP00000425841.1
WDR70	ENST00000511906.5	n.476G>T		non_coding_transcript_exon_variant	4/15	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 12, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	0.33
DANN	Benign	0.36
DEOGEN2	Benign	0.017	T;.
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.072	N
LIST_S2	Benign	0.34	T;T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.039	T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	-1.4	N;.
PrimateAI	Benign	0.38	T
PROVEAN	Benign	1.3	N;N
REVEL	Benign	0.17
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;B
Vest4		0.21
MutPred		0.27		Loss of helix (P = 0.4763);Loss of helix (P = 0.4763);
MVP		0.093
MPC		0.38
ClinPred		0.039	T
GERP RS		-1.9
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		3.9
Varity_R		0.023
gMVP		0.16

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: chr5-37396642;