rs2014029

Positions:

• chr1-212075594-T-A
• chr1-212075594-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016448.4(DTL):​c.1036-2579T>A variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DTL NM_016448.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0880

Genes affected

DTL (HGNC:30288): (denticleless E3 ubiquitin protein ligase homolog) Contributes to ubiquitin-protein transferase activity. Involved in several processes, including protein ubiquitination; regulation of G2/M transition of mitotic cell cycle; and translesion synthesis. Located in centrosome; cytosol; and nuclear lumen. Part of Cul4A-RING E3 ubiquitin ligase complex and Cul4B-RING E3 ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DTL	NM_016448.4	c.1036-2579T>A		intron_variant		ENST00000366991.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DTL	ENST00000366991.5	c.1036-2579T>A		intron_variant		1	NM_016448.4	P1
DTL	ENST00000542077.5	c.910-2579T>A		intron_variant		2
DTL	ENST00000475419.5	n.851-2579T>A		intron_variant, non_coding_transcript_variant		2
DTL	ENST00000489149.1	n.141-2579T>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	11
DANN	Benign	0.86

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: rs2014029; hg19: chr1-212248936;