NM_001161476.3:c.840C>A

Variant names:

• chr14-100468038-C-A
• rs796052162
• NM_001161476.3:c.840C>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP6

The NM_001161476.3(WDR25):​c.840C>A​(p.Asp280Glu) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: WDR25 NM_001161476.3 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.18
• Publications: 1 publications found

Genes affected

WDR25 (HGNC:21064): (WD repeat domain 25) This gene encodes a protein containing 7 WD repeats. WD repeats are approximately 30 to 40-amino acid domains containing several conserved residues, typically having a Tryptophan-Aspartic acid dipeptide (WD) at the C-terminal end. WD domains are involved in protein-protein interactions in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2017]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1509611).
• BP6: Variant 14-100468038-C-A is Benign according to our data. Variant chr14-100468038-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 207867.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001161476.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR25	NM_001161476.3	MANE Select	c.840C>A	p.Asp280Glu	missense	Exon 3 of 7	NP_001154948.1
	WDR25	NM_001350947.2		c.840C>A	p.Asp280Glu	missense	Exon 3 of 7	NP_001337876.1
	WDR25	NM_001350948.2		c.840C>A	p.Asp280Glu	missense	Exon 3 of 7	NP_001337877.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR25	ENST00000402312.8	TSL:2 MANE Select	c.840C>A	p.Asp280Glu	missense	Exon 3 of 7	ENSP00000385540.3
	WDR25	ENST00000335290.10	TSL:1	c.840C>A	p.Asp280Glu	missense	Exon 3 of 7	ENSP00000334148.6
	WDR25	ENST00000542471.2	TSL:1	c.69C>A	p.Asp23Glu	missense	Exon 2 of 6	ENSP00000441903.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

Long QT syndrome Benign:1

Medical Research Institute, Tokyo Medical and Dental University

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: research

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	16
DANN	Benign	0.80
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.28	N
PhyloP100		1.2
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.077
Sift	Benign	0.16	T
Sift4G	Benign	0.19	T
Polyphen		0.80	P
Vest4		0.39
MutPred		0.45		Gain of sheet (P = 0.0827)
MVP		0.31
MPC		0.13
ClinPred		0.41	T
GERP RS		4.1
Varity_R		0.048
gMVP		0.13
Mutation Taster		=87/13	polymorphism

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

Other links and lift over

dbSNP: rs796052162; hg19: chr14-100934375;