rs777638253
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP6BS2
The NM_003482.4(KMT2D):c.10522C>T(p.Arg3508Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000026 in 1,612,764 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R3508Q) 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 -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KMT2D | NM_003482.4 | c.10522C>T | p.Arg3508Trp | missense_variant | 39/55 | ENST00000301067.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KMT2D | ENST00000301067.12 | c.10522C>T | p.Arg3508Trp | missense_variant | 39/55 | 5 | NM_003482.4 | A2 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152110Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000362 AC: 9AN: 248766Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 134968
GnomAD4 exome AF: 0.0000253 AC: 37AN: 1460654Hom.: 0 Cov.: 33 AF XY: 0.0000179 AC XY: 13AN XY: 726450
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152110Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74304
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 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Feb 10, 2023 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Kabuki syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Aug 30, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at