GeneBe

NM_000722.4:c.355-9_355-5dupTTTTT

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000722.4(CACNA2D1):​c.355-9_355-5dupTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 30)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

CACNA2D1
NM_000722.4 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0210

Publications

1 publications found
Variant links:
Genes affected
CACNA2D1 (HGNC:1399): (calcium voltage-gated channel auxiliary subunit alpha2delta 1) The preproprotein encoded by this gene is cleaved into multiple chains that comprise the alpha-2 and delta subunits of the voltage-dependent calcium channel complex. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization. Mutations in this gene can cause cardiac deficiencies, including Brugada syndrome and short QT syndrome. Alternate splicing results in multiple transcript variants, some of which may lack the delta subunit portion. [provided by RefSeq, Nov 2014]
CACNA2D1 Gene-Disease associations (from GenCC):
  • short QT syndrome
    Inheritance: AD Classification: SUPPORTIVE, NO_KNOWN Submitted by: ClinGen, Orphanet
  • Brugada syndrome
    Inheritance: AD, Unknown Classification: LIMITED, NO_KNOWN Submitted by: Ambry Genetics, Genomics England PanelApp
  • genetic developmental and epileptic encephalopathy
    Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
  • developmental and epileptic encephalopathy 110
    Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
  • Brugada syndrome 1
    Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CACNA2D1NM_000722.4 linkc.355-9_355-5dupTTTTT splice_region_variant, intron_variant Intron 4 of 38 ENST00000356860.8 NP_000713.2 P54289-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CACNA2D1ENST00000356860.8 linkc.355-5_355-4insTTTTT splice_region_variant, intron_variant Intron 4 of 38 1 NM_000722.4 ENSP00000349320.3 P54289-2

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1190326
Hom.:
0
Cov.:
25
AF XY:
0.00
AC XY:
0
AN XY:
589952
African (AFR)
AF:
0.00
AC:
0
AN:
27294
American (AMR)
AF:
0.00
AC:
0
AN:
32526
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
20552
East Asian (EAS)
AF:
0.00
AC:
0
AN:
31730
South Asian (SAS)
AF:
0.00
AC:
0
AN:
65808
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
37974
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4832
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
920792
Other (OTH)
AF:
0.00
AC:
0
AN:
48818
GnomAD4 genome
Cov.:
30
Alfa
AF:
0.000159
Hom.:
11

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
0.021

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs142849270; hg19: chr7-81765996; API