12-8604926-CAAAAAAAAA-C

Variant names:

• chr12-8604926-CAAAAAAAAA-C
• NM_020661.4:c.428-13_428-5delTTTTTTTTT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020661.4(AICDA):​c.428-13_428-5delTTTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000056 in 1,249,680 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: 0.0000056 (0 hom.)
• Consequence: AICDA NM_020661.4 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.61

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 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
AICDA	NM_020661.4	c.428-13_428-5delTTTTTTTTT		splice_region_variant, intron_variant	Intron 3 of 4	ENST00000229335.11	NP_065712.1
AICDA	NM_001330343.2	c.428-43_428-35delTTTTTTTTT		intron_variant	Intron 3 of 4		NP_001317272.1
AICDA	NM_001410970.1	c.427+280_427+288delTTTTTTTTT		intron_variant	Intron 3 of 3		NP_001397899.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AICDA	ENST00000229335.11	c.428-13_428-5delTTTTTTTTT		splice_region_variant, intron_variant	Intron 3 of 4	1	NM_020661.4	ENSP00000229335.6

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000560 AC: 7 AN: 1249680 Hom.: 0 AF XY: 0.00000803 AC XY: 5 AN XY: 622912

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000730

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-8757522;