14-89955920-G-GGCC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000393452.7(TDP1):c.-276_-274dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0729 in 152,408 control chromosomes in the GnomAD database, including 714 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.073 (714 hom., cov: 32)
  • Exomes 𝑓: 0.057 (0 hom.)
• Consequence: TDP1 ENST00000393452.7 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.523

Genes affected

TDP1 (HGNC:18884): (tyrosyl-DNA phosphodiesterase 1) The protein encoded by this gene is involved in repairing stalled topoisomerase I-DNA complexes by catalyzing the hydrolysis of the phosphodiester bond between the tyrosine residue of topoisomerase I and the 3-prime phosphate of DNA. This protein may also remove glycolate from single-stranded DNA containing 3-prime phosphoglycolate, suggesting a role in repair of free-radical mediated DNA double-strand breaks. This gene is a member of the phospholipase D family and contains two PLD phosphodiesterase domains. Mutations in this gene are associated with the disease spinocerebellar ataxia with axonal neuropathy (SCAN1). [provided by RefSeq, Aug 2016]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 14-89955920-G-GGCC is Benign according to our data. Variant chr14-89955920-G-GGCC is described in ClinVar as [Benign]. Clinvar id is 314811.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TDP1	NM_018319.4			upstream_gene_variant		ENST00000335725.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TDP1	ENST00000335725.9			upstream_gene_variant		1	NM_018319.4	P1

Frequencies

GnomAD3 genomes AF: 0.0728 AC: 11081 AN: 152164 Hom.: 709 Cov.: 32

Gnomad AFR AF: 0.0162

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.0507

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.0754

Gnomad MID AF: 0.0510

Gnomad NFE AF: 0.0639

Gnomad OTH AF: 0.0778

GnomAD4 exome AF: 0.0574 AC: 7 AN: 122 Hom.: 0 Cov.: 0 AF XY: 0.0556 AC XY: 5 AN XY: 90

Gnomad4 AFR exome AF: 0.00

Gnomad4 NFE exome AF: 0.0566

Gnomad4 OTH exome AF: 0.100

GnomAD4 genome AF: 0.0729 AC: 11107 AN: 152286 Hom.: 714 Cov.: 32 AF XY: 0.0804 AC XY: 5990 AN XY: 74468

Gnomad4 AFR AF: 0.0162

Gnomad4 AMR AF: 0.184

Gnomad4 ASJ AF: 0.0507

Gnomad4 EAS AF: 0.200

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.0754

Gnomad4 NFE AF: 0.0639

Gnomad4 OTH AF: 0.0813

Alfa AF: 0.0680 Hom.: 56

Asia WGS AF: 0.210 AC: 727 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Autosomal recessive cerebellar ataxia Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs35210768; hg19: chr14-90422264;