chr5-140671528-T-G

Variant names:

• chr5-140671528-T-G
• NM_194249.3:c.827A>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_194249.3(DND1):​c.827A>C​(p.Lys276Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,423,710 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DND1 NM_194249.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.22

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

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 rank	MANE	Protein	UniProt
DND1	NM_194249.3	c.827A>C	p.Lys276Thr	missense_variant	Exon 4 of 4	ENST00000542735.2	NP_919225.1
WDR55	NM_017706.5	c.*1874T>G		3_prime_UTR_variant	Exon 7 of 7	ENST00000358337.10	NP_060176.3
WDR55	XM_005268469.4	c.*296T>G		3_prime_UTR_variant	Exon 8 of 8		XP_005268526.1
WDR55	XM_017009600.3	c.*1874T>G		3_prime_UTR_variant	Exon 8 of 8		XP_016865089.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DND1	ENST00000542735.2	c.827A>C	p.Lys276Thr	missense_variant	Exon 4 of 4	1	NM_194249.3	ENSP00000445366.1
WDR55	ENST00000358337.10	c.*1874T>G		3_prime_UTR_variant	Exon 7 of 7	1	NM_017706.5	ENSP00000351100.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1423710 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 705448

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000183

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.79	T
M_CAP	Uncertain	0.091	D
MetaRNN	Uncertain	0.63	D
MetaSVM	Benign	-0.36	T
MutationAssessor	Benign	1.0	L
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-2.1	N
REVEL	Uncertain	0.33
Sift	Uncertain	0.022	D
Sift4G	Uncertain	0.043	D
Polyphen		1.0	D
Vest4		0.64
MutPred		0.46		Loss of methylation at K276 (P = 0.0014);
MVP		0.63
MPC		1.9
ClinPred		0.92	D
GERP RS		5.4
Varity_R		0.22
gMVP		0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr5-140051113; COSMIC: COSV56908501; COSMIC: COSV56908501;