5-37392080-A-G

Position:

• chr5-37392080-A-G

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.256A>G​(p.Arg86Gly) 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: 32)
• Consequence: WDR70 NM_018034.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.43

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]

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=0.03316143).
• BP6: Variant 5-37392080-A-G is Benign according to our data. Variant chr5-37392080-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3332915.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR70	NM_018034.4	c.256A>G	p.Arg86Gly	missense_variant	4/18	ENST00000265107.9
WDR70	NM_001345998.2	c.253A>G	p.Arg85Gly	missense_variant	4/18
WDR70	NM_001345999.2	c.190A>G	p.Arg64Gly	missense_variant	3/17
WDR70	XM_047417348.1	c.187A>G	p.Arg63Gly	missense_variant	3/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR70	ENST00000265107.9	c.256A>G	p.Arg86Gly	missense_variant	4/18	1	NM_018034.4	P1
WDR70	ENST00000504564.1	c.256A>G	p.Arg86Gly	missense_variant	4/12	1
WDR70	ENST00000511906.5	n.270A>G		non_coding_transcript_exon_variant	3/15	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Apr 06, 2024

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	0.060
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	14
DANN	Benign	0.72
DEOGEN2	Benign	0.021	T;.
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.56	T;T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.033	T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	-1.7	N;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.020	N;N
REVEL	Benign	0.19
Sift	Benign	0.25	T;T
Sift4G	Benign	0.27	T;T
Polyphen		0.0	B;B
Vest4		0.069
MutPred		0.20		Loss of MoRF binding (P = 0.0341);Loss of MoRF binding (P = 0.0341);
MVP		0.043
MPC		0.54
ClinPred		0.048	T
GERP RS		-0.083
Varity_R		0.039
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

LitVar

Other links and lift over

dbSNP: rs1275930268; hg19: chr5-37392182;