rs767801199
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3
The NM_032737.4(LMNB2):c.742C>T(p.Arg248Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000199 in 1,608,600 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R248Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_032737.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LMNB2 | NM_032737.4 | c.742C>T | p.Arg248Trp | missense_variant | 5/12 | ENST00000325327.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LMNB2 | ENST00000325327.4 | c.742C>T | p.Arg248Trp | missense_variant | 5/12 | 1 | NM_032737.4 | P1 | |
LMNB2 | ENST00000527409.1 | n.378C>T | non_coding_transcript_exon_variant | 2/4 | 5 | ||||
LMNB2 | ENST00000534495.1 | n.380C>T | non_coding_transcript_exon_variant | 2/2 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000591 AC: 9AN: 152174Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000123 AC: 3AN: 243004Hom.: 0 AF XY: 0.00000754 AC XY: 1AN XY: 132620
GnomAD4 exome AF: 0.0000158 AC: 23AN: 1456308Hom.: 0 Cov.: 39 AF XY: 0.0000152 AC XY: 11AN XY: 724726
GnomAD4 genome AF: 0.0000591 AC: 9AN: 152292Hom.: 0 Cov.: 33 AF XY: 0.0000537 AC XY: 4AN XY: 74474
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 10, 2023 | The c.682C>T (p.R228W) alteration is located in exon 5 (coding exon 5) of the LMNB2 gene. This alteration results from a C to T substitution at nucleotide position 682, causing the arginine (R) at amino acid position 228 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Lipodystrophy, partial, acquired, susceptibility to;C4225289:Progressive myoclonic epilepsy type 9 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 18, 2023 | This variant has not been reported in the literature in individuals affected with LMNB2-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 248 of the LMNB2 protein (p.Arg248Trp). ClinVar contains an entry for this variant (Variation ID: 576218). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt LMNB2 protein function. - |
Progressive myoclonic epilepsy type 9 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | New York Genome Center | Jul 09, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at