12-49041265-C-T
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2
The NM_003482.4(KMT2D):c.6505G>A(p.Ala2169Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,517,160 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★).
Frequency
Consequence
NM_003482.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KMT2D | NM_003482.4 | c.6505G>A | p.Ala2169Thr | missense_variant | 32/55 | ENST00000301067.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KMT2D | ENST00000301067.12 | c.6505G>A | p.Ala2169Thr | missense_variant | 32/55 | 5 | NM_003482.4 | A2 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 151954Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.0000103 AC: 14AN: 1365206Hom.: 0 Cov.: 35 AF XY: 0.0000104 AC XY: 7AN XY: 670134
GnomAD4 genome AF: 0.0000132 AC: 2AN: 151954Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2AN XY: 74196
ClinVar
Submissions by phenotype
Kabuki syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 16, 2023 | 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 KMT2D protein function. ClinVar contains an entry for this variant (Variation ID: 134694). This variant has not been reported in the literature in individuals affected with KMT2D-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 alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 2169 of the KMT2D protein (p.Ala2169Thr). - |
not specified Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at