rs397516744
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_002294.3(LAMP2):c.371C>T(p.Thr124Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000101 in 1,093,006 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. T124T) has been classified as Likely benign.
Frequency
Consequence
NM_002294.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMP2 | NM_002294.3 | c.371C>T | p.Thr124Ile | missense_variant | 3/9 | ENST00000200639.9 | |
LAMP2 | NM_001122606.1 | c.371C>T | p.Thr124Ile | missense_variant | 3/9 | ||
LAMP2 | NM_013995.2 | c.371C>T | p.Thr124Ile | missense_variant | 3/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMP2 | ENST00000200639.9 | c.371C>T | p.Thr124Ile | missense_variant | 3/9 | 1 | NM_002294.3 | P3 | |
LAMP2 | ENST00000434600.6 | c.371C>T | p.Thr124Ile | missense_variant | 3/9 | 1 | A1 | ||
LAMP2 | ENST00000371335.4 | c.371C>T | p.Thr124Ile | missense_variant | 3/9 | 1 | A1 | ||
LAMP2 | ENST00000706600.1 | c.371C>T | p.Thr124Ile | missense_variant | 3/9 |
Frequencies
GnomAD3 genomes ? Cov.: 21
GnomAD4 exome AF: 0.0000101 AC: 11AN: 1093006Hom.: 0 Cov.: 29 AF XY: 0.00000279 AC XY: 1AN XY: 358626
GnomAD4 genome ? Cov.: 21
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 22, 2012 | Variant classified as Uncertain Significance - Favor Benign. The Thr124Ile varia nt in LAMP2 has not been previously reported, but has previously been identified in one individual with HCM by our laboratory. This variant has not been identif ied in large and broad populations by the NHLBI Exome Sequencing Project (http:/ /evs.gs.washington.edu/EVS). This low frequency supports a pathogenic role. Howe ver, threonine (Thr) at position 124 is not conserved in mammals or chicken, red ucing the likelihood that the change is pathogenic. In addition, pathogenic miss ense variants are rare in the LAMP2 gene, as most disease causing variants lead to a loss of function. Computational analyses (biochemical amino acid properties , AlignGVGD, PolyPhen2, and SIFT) suggest that the Thr124Ile variant may not imp act the protein, though this information is not predictive enough to rule out pa thogenicity. In summary, although this data suggests that the Thr124Ile variant is likely benign, in the absence of additional information its clinical signific ance cannot be determined. - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 07, 2020 | The c.371C>T (p.T124I) alteration is located in exon 3 (coding exon 3) of the LAMP2 gene. This alteration results from a C to T substitution at nucleotide position 371, causing the threonine (T) at amino acid position 124 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at