chr19-13298647-G-GGCCCTC
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM4BP6BS1BS2
The NM_001127222.2(CACNA1A):c.2985_2986insGAGGGC(p.Glu994_Gly995dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000218 in 1,517,446 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. G995G) has been classified as Likely benign.
Frequency
Consequence
NM_001127222.2 inframe_insertion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA1A | NM_001127222.2 | c.2985_2986insGAGGGC | p.Glu994_Gly995dup | inframe_insertion | 19/47 | ENST00000360228.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA1A | ENST00000360228.11 | c.2985_2986insGAGGGC | p.Glu994_Gly995dup | inframe_insertion | 19/47 | 1 | NM_001127222.2 |
Frequencies
GnomAD3 genomes ? AF: 0.000592 AC: 90AN: 151922Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000105 AC: 12AN: 114332Hom.: 0 AF XY: 0.0000962 AC XY: 6AN XY: 62386
GnomAD4 exome AF: 0.000177 AC: 241AN: 1365414Hom.: 0 Cov.: 32 AF XY: 0.000169 AC XY: 114AN XY: 673334
GnomAD4 genome ? AF: 0.000592 AC: 90AN: 152032Hom.: 0 Cov.: 33 AF XY: 0.000525 AC XY: 39AN XY: 74306
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:3
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 15, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2023 | CACNA1A: BS1, BS2 - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Oct 23, 2014 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | May 21, 2018 | - - |
Developmental and epileptic encephalopathy, 42 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | May 08, 2018 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Episodic ataxia type 2;C4310716:Developmental and epileptic encephalopathy, 42 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 03, 2019 | This alteration is classified as 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. - |
CACNA1A-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 14, 2021 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at