chr5-140671580-G-C

Variant names:

• chr5-140671580-G-C
• NM_194249.3:c.775C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_194249.3(DND1):​c.775C>G​(p.Leu259Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: DND1 NM_194249.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.38
• Publications: 0 publications found

Genes affected

DND1 (HGNC:23799): (DND microRNA-mediated repression inhibitor 1) This gene encodes a protein that binds to microRNA-targeting sequences of mRNAs, inhibiting microRNA-mediated repression. Reduced expression of this gene has been implicated in tongue squamous cell carcinoma. Two pseudogenes of this gene are located on the long arm of chromosome 17. [provided by RefSeq, Dec 2010]

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_194249.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DND1	NM_194249.3	MANE Select	c.775C>G	p.Leu259Val	missense	Exon 4 of 4	NP_919225.1	Q8IYX4
	WDR55	NM_017706.5	MANE Select	c.*1926G>C		3_prime_UTR	Exon 7 of 7	NP_060176.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DND1	ENST00000542735.2	TSL:1 MANE Select	c.775C>G	p.Leu259Val	missense	Exon 4 of 4	ENSP00000445366.1	Q8IYX4
	WDR55	ENST00000358337.10	TSL:1 MANE Select	c.*1926G>C		3_prime_UTR	Exon 7 of 7	ENSP00000351100.5	Q9H6Y2-1
	WDR55	ENST00000506393.5	TSL:2	n.*1254G>C		non_coding_transcript_exon	Exon 6 of 6	ENSP00000426304.1	D6RGJ8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.083	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.37	T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.17
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.76	T
M_CAP	Uncertain	0.20	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Uncertain	-0.28	T
MutationAssessor	Benign	1.1	L
PhyloP100		2.4
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.83	N
REVEL	Uncertain	0.44
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.0090	D
Polyphen		1.0	D
Vest4		0.40
MutPred		0.37		Gain of MoRF binding (P = 0.0766)
MVP		0.76
MPC		1.8
ClinPred		0.83	D
GERP RS		1.4
Varity_R		0.11
gMVP		0.90
Mutation Taster		=55/45	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

hg19: chr5-140051165;