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rs730882208

chr11-1753572-G-GATGAAGACGTCGCCC

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PM4PP5

The NM_001909.5(CTSD):c.1169_1170insGGGCGACGTCTTCAT(p.Phe389_Ile390insMetGlyAspValPhe) variant causes a inframe insertion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. I390I) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Consequence

CTSD
NM_001909.5 inframe_insertion

Scores

Not classified

Clinical Significance

Likely pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 6.95
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
PM4
?
    PM4 - Protein length changes as a result of in-frame deletions/insertions in a nonrepeat region or stop-loss variants
Nonframeshift variant in NON repetitive region in NM_001909.5.
PP5
?
    PP5 - Reputable source recently reports variant as pathogenic, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 11-1753572-G-GATGAAGACGTCGCCC is Pathogenic according to our data. Variant chr11-1753572-G-GATGAAGACGTCGCCC is described in ClinVar as [Likely_pathogenic]. Clinvar id is 183293.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CTSDNM_001909.5 linkuse as main transcriptc.1169_1170insGGGCGACGTCTTCAT p.Phe389_Ile390insMetGlyAspValPhe inframe_insertion 9/9 ENST00000236671.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CTSDENST00000236671.7 linkuse as main transcriptc.1169_1170insGGGCGACGTCTTCAT p.Phe389_Ile390insMetGlyAspValPhe inframe_insertion 9/91 NM_001909.5 P2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
Cov.:
33
GnomAD4 exome
Cov.:
33
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
Cov.:
33

ClinVar

Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Exaggerated startle response;CN228309:Severe microlissencephaly Pathogenic:1
Likely pathogenic, no assertion criteria providedresearchDepartment Of Translational Genomics (developmental Genetics Section), King Faisal Specialist Hospital & Research CentreDec 01, 2014- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs730882208; hg19: chr11-1774802; API