5-140671580-G-C

Position:

• chr5-140671580-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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

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]

WDR55 (HGNC:):

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
DND1	NM_194249.3	c.775C>G	p.Leu259Val	missense_variant	4/4	ENST00000542735.2	NP_919225.1
WDR55	NM_017706.5	c.*1926G>C		3_prime_UTR_variant	7/7	ENST00000358337.10	NP_060176.3
WDR55	XM_005268469.4	c.*348G>C		3_prime_UTR_variant	8/8		XP_005268526.1
WDR55	XM_017009600.3	c.*1926G>C		3_prime_UTR_variant	8/8		XP_016865089.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DND1	ENST00000542735.2	c.775C>G	p.Leu259Val	missense_variant	4/4	1	NM_194249.3	ENSP00000445366.1
WDR55	ENST00000358337.10	c.*1926G>C		3_prime_UTR_variant	7/7	1	NM_017706.5	ENSP00000351100.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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

Jul 27, 2024

The c.775C>G (p.L259V) alteration is located in exon 4 (coding exon 4) of the DND1 gene. This alteration results from a C to G substitution at nucleotide position 775, causing the leucine (L) at amino acid position 259 to be replaced by a valine (V). 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	0.16
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
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

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: chr5-140051165;