rs770692765
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 1P and 3B. PP2BP4_ModerateBP6
The NM_003482.4(KMT2D):c.6608C>T(p.Thr2203Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000355 in 1,521,340 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T2203S) has been classified as Likely benign.
Frequency
Consequence
NM_003482.4 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 |
---|---|---|---|---|---|---|---|
KMT2D | NM_003482.4 | c.6608C>T | p.Thr2203Met | missense_variant | 32/55 | ENST00000301067.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KMT2D | ENST00000301067.12 | c.6608C>T | p.Thr2203Met | missense_variant | 32/55 | 5 | NM_003482.4 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152036Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000183 AC: 3AN: 163898Hom.: 0 AF XY: 0.0000229 AC XY: 2AN XY: 87458
GnomAD4 exome AF: 0.0000365 AC: 50AN: 1369304Hom.: 0 Cov.: 35 AF XY: 0.0000312 AC XY: 21AN XY: 672248
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152036Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74238
ClinVar
Submissions by phenotype
Kabuki syndrome 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Human Genetics, Inc, Center for Human Genetics, Inc | Nov 01, 2016 | - - |
Kabuki syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 06, 2023 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 21, 2021 | See Variant Classification Assertion Criteria. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at