GeneBe

chr12-8604926-C-CAAAAA

Variant names:

Variant summary

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

The NM_020661.4(AICDA):​c.428-9_428-5dupTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000008 in 1,249,666 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 0)
Exomes 𝑓: 8.0e-7 ( 0 hom. )

Consequence

AICDA
NM_020661.4 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.227

Publications

0 publications found
Variant links:
Genes affected
AICDA (HGNC:13203): (activation induced cytidine deaminase) This gene encodes a RNA-editing deaminase that is a member of the cytidine deaminase family. AICDA is specifically expressed and active in germinal center-like B cells. In the germinal center, AICDA is involved in somatic hypermutation, gene conversion, and class-switch recombination of immunoglobulin genes. An epigenetic role in neoplastic transformation and lymphoma progression has been experimentally ascribed to AICDA using mouse models. Defects in this gene are the cause of autosomal recessive hyper-IgM immunodeficiency syndrome type 2 (HIGM2). [provided by RefSeq, Jul 2020]
AICDA Gene-Disease associations (from GenCC):
  • hyper-IgM syndrome type 2
    Inheritance: AD, AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)

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
AICDANM_020661.4 linkc.428-9_428-5dupTTTTT splice_region_variant, intron_variant Intron 3 of 4 ENST00000229335.11 NP_065712.1 Q9GZX7-1Q546Y9Q7Z599
AICDANM_001330343.2 linkc.428-39_428-35dupTTTTT intron_variant Intron 3 of 4 NP_001317272.1 Q9GZX7-2Q7Z599
AICDANM_001410970.1 linkc.427+284_427+288dupTTTTT intron_variant Intron 3 of 3 NP_001397899.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
AICDAENST00000229335.11 linkc.428-9_428-5dupTTTTT splice_region_variant, intron_variant Intron 3 of 4 1 NM_020661.4 ENSP00000229335.6 Q9GZX7-1

Frequencies

GnomAD3 genomes
Cov.:
0
GnomAD4 exome
AF:
8.00e-7
AC:
1
AN:
1249666
Hom.:
0
Cov.:
34
AF XY:
0.00000161
AC XY:
1
AN XY:
622902
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
29126
American (AMR)
AF:
0.00
AC:
0
AN:
33050
Ashkenazi Jewish (ASJ)
AF:
0.0000449
AC:
1
AN:
22258
East Asian (EAS)
AF:
0.00
AC:
0
AN:
33854
South Asian (SAS)
AF:
0.00
AC:
0
AN:
73712
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
43106
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
3618
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
959100
Other (OTH)
AF:
0.00
AC:
0
AN:
51842
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
0.23

Splicing

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

Publications

Other links and lift over

dbSNP: rs5796316; hg19: chr12-8757522; API