rs386833838
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_002299.4(LCT):c.653_654delCT(p.Ser218CysfsTer6) variant causes a frameshift change. The variant allele was found at a frequency of 0.000000684 in 1,461,702 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 29)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
LCT
NM_002299.4 frameshift
NM_002299.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.82
Publications
6 publications found
Genes affected
LCT (HGNC:6530): (lactase) The protein encoded by this gene belongs to the glycosyl hydrolase 1 family of proteins. The encoded preproprotein is proteolytically processed to generate the mature enzyme. This enzyme is integral to the plasma membrane and has both phlorizin hydrolase activity and lactase activity. Mutations in this gene are associated with congenital lactase deficiency. Polymorphisms in this gene are associated with lactase persistence, in which intestinal lactase activity persists at childhood levels into adulthood. [provided by RefSeq, Jan 2016]
LCT Gene-Disease associations (from GenCC):
- congenital lactase deficiencyInheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 11 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 2-135833176-CAG-C is Pathogenic according to our data. Variant chr2-135833176-CAG-C is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 56393.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| LCT | ENST00000264162.7 | c.653_654delCT | p.Ser218CysfsTer6 | frameshift_variant | Exon 2 of 17 | 1 | NM_002299.4 | ENSP00000264162.2 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
29
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461702Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 727164 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1461702
Hom.:
AF XY:
AC XY:
1
AN XY:
727164
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33474
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26132
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86252
European-Finnish (FIN)
AF:
AC:
0
AN:
53418
Middle Eastern (MID)
AF:
AC:
0
AN:
5764
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1111852
Other (OTH)
AF:
AC:
0
AN:
60386
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
29
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Congenital lactase deficiency Pathogenic:1
-
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM)
Significance:Likely pathogenic
Review Status:no assertion criteria provided
Collection Method:literature only
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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