2-135817629-G-T
Variant names:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_002299.4(LCT):c.1419C>A(p.Gly473Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 1,613,654 control chromosomes in the GnomAD database, including 395,312 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.51 ( 24069 hom., cov: 33)
Exomes 𝑓: 0.69 ( 371243 hom. )
Consequence
LCT
NM_002299.4 synonymous
NM_002299.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.54
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
Variant 2-135817629-G-T is Benign according to our data. Variant chr2-135817629-G-T is described in ClinVar as [Benign]. Clinvar id is 331202.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-135817629-G-T is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-3.54 with no splicing effect.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.512 AC: 77763AN: 152018Hom.: 24068 Cov.: 33
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GnomAD3 exomes AF: 0.558 AC: 140065AN: 250814Hom.: 44250 AF XY: 0.559 AC XY: 75857AN XY: 135650
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GnomAD4 exome AF: 0.691 AC: 1009374AN: 1461518Hom.: 371243 Cov.: 51 AF XY: 0.679 AC XY: 493777AN XY: 727084
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GnomAD4 genome AF: 0.511 AC: 77765AN: 152136Hom.: 24069 Cov.: 33 AF XY: 0.503 AC XY: 37360AN XY: 74338
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ClinVar
Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
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Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided
- -
Feb 03, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Nov 12, 2018
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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not specified Benign:2
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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing
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Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing
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Lactose intolerance Benign:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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Congenital lactase deficiency Benign:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at