11-1753290-GGA-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001909.5(CTSD):c.*211_*212del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0127 in 633,750 control chromosomes in the GnomAD database, including 87 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (18 hom., cov: 33)
  • Exomes 𝑓: 0.013 (69 hom.)
• Consequence: CTSD NM_001909.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.846

Genes affected

CTSD (HGNC:2529): (cathepsin D) This gene encodes a member of the A1 family of peptidases. The encoded preproprotein is proteolytically processed to generate multiple protein products. These products include the cathepsin D light and heavy chains, which heterodimerize to form the mature enzyme. This enzyme exhibits pepsin-like activity and plays a role in protein turnover and in the proteolytic activation of hormones and growth factors. Mutations in this gene play a causal role in neuronal ceroid lipofuscinosis-10 and may be involved in the pathogenesis of several other diseases, including breast cancer and possibly Alzheimer's disease. [provided by RefSeq, Nov 2015]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 11-1753290-GGA-G is Benign according to our data. Variant chr11-1753290-GGA-G is described in ClinVar as [Likely_benign]. Clinvar id is 1200404.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0116 (1765/152310) while in subpopulation NFE AF= 0.0156 (1060/68014). AF 95% confidence interval is 0.0148. There are 18 homozygotes in gnomad4. There are 874 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTSD	NM_001909.5	c.*211_*212del		3_prime_UTR_variant	9/9	ENST00000236671.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTSD	ENST00000236671.7	c.*211_*212del		3_prime_UTR_variant	9/9	1	NM_001909.5	P2

Frequencies

GnomAD3 genomes AF: 0.0116 AC: 1766 AN: 152192 Hom.: 18 Cov.: 33

Gnomad AFR AF: 0.00212

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0107

Gnomad ASJ AF: 0.0193

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.0317

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0156

Gnomad OTH AF: 0.0162

GnomAD4 exome AF: 0.0131 AC: 6308 AN: 481440 Hom.: 69 AF XY: 0.0126 AC XY: 3232 AN XY: 256268

Gnomad4 AFR exome AF: 0.00214

Gnomad4 AMR exome AF: 0.00832

Gnomad4 ASJ exome AF: 0.0159

Gnomad4 EAS exome AF: 0.0000322

Gnomad4 SAS exome AF: 0.00183

Gnomad4 FIN exome AF: 0.0312

Gnomad4 NFE exome AF: 0.0154

Gnomad4 OTH exome AF: 0.0139

GnomAD4 genome AF: 0.0116 AC: 1765 AN: 152310 Hom.: 18 Cov.: 33 AF XY: 0.0117 AC XY: 874 AN XY: 74468

Gnomad4 AFR AF: 0.00212

Gnomad4 AMR AF: 0.0107

Gnomad4 ASJ AF: 0.0193

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00103

Gnomad4 FIN AF: 0.0317

Gnomad4 NFE AF: 0.0156

Gnomad4 OTH AF: 0.0161

Alfa AF: 0.0157 Hom.: 2

Bravo AF: 0.00934

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 2018

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Computational scores

Source: dbNSFP v4.3

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: rs199970387; hg19: chr11-1774520;