chr11-118436526-G-C
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2
The NM_001197104.2(KMT2A):āc.14G>Cā(p.Cys5Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000634 in 1,262,236 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_001197104.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KMT2A | ENST00000534358.8 | c.14G>C | p.Cys5Ser | missense_variant | Exon 1 of 36 | 1 | NM_001197104.2 | ENSP00000436786.2 | ||
ENSG00000285827 | ENST00000648261.1 | c.-798-32249G>C | intron_variant | Intron 1 of 6 | ENSP00000498126.1 |
Frequencies
GnomAD3 genomes AF: 0.00000660 AC: 1AN: 151594Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000630 AC: 7AN: 1110642Hom.: 0 Cov.: 25 AF XY: 0.00000567 AC XY: 3AN XY: 529374
GnomAD4 genome AF: 0.00000660 AC: 1AN: 151594Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74052
ClinVar
Submissions by phenotype
not provided Uncertain:2
This sequence change replaces cysteine, which is neutral and slightly polar, with serine, which is neutral and polar, at codon 5 of the KMT2A protein (p.Cys5Ser). 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 1312973). This variant has not been reported in the literature in individuals affected with KMT2A-related conditions. This variant is not present in population databases (gnomAD no frequency). -
Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at