rs372198586
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 1P and 14B. PP2BP4_ModerateBP6_Very_StrongBS2
The NM_012281.3(KCND2):c.1534C>T(p.Pro512Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,613,584 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P512L) has been classified as Uncertain significance.
Frequency
Consequence
NM_012281.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCND2 | NM_012281.3 | c.1534C>T | p.Pro512Ser | missense_variant | 5/6 | ENST00000331113.9 | |
KCND2 | XM_047420346.1 | c.1534C>T | p.Pro512Ser | missense_variant | 6/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCND2 | ENST00000331113.9 | c.1534C>T | p.Pro512Ser | missense_variant | 5/6 | 1 | NM_012281.3 | P1 | |
KCND2 | ENST00000425288.1 | c.292C>T | p.Pro98Ser | missense_variant | 4/5 | 4 | |||
KCND2 | ENST00000473190.1 | n.349C>T | non_coding_transcript_exon_variant | 2/3 | 4 |
Frequencies
GnomAD3 genomes AF: 0.000131 AC: 20AN: 152174Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000319 AC: 8AN: 250738Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135482
GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461410Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7AN XY: 727000
GnomAD4 genome AF: 0.000131 AC: 20AN: 152174Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 10AN XY: 74316
ClinVar
Submissions by phenotype
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 28, 2024 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Early myoclonic encephalopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at