12-8604926-CAAAAAAAAA-CAAA

Variant names:

• chr12-8604926-CAAAAAA-C
• rs5796316
• NM_020661.4:c.428-10_428-5delTTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_020661.4(AICDA):​c.428-10_428-5delTTTTTT 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 1,249,680 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 8.0e-7 (0 hom.)
• Consequence: AICDA NM_020661.4 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.61
• Publications: 0 publications found

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, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 12-8604926-CAAAAAA-C is Benign according to our data. Variant chr12-8604926-CAAAAAA-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1666461.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020661.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AICDA	NM_020661.4	MANE Select	c.428-10_428-5delTTTTTT		splice_region intron	N/A	NP_065712.1	Q9GZX7-1
	AICDA	NM_001330343.2		c.428-40_428-35delTTTTTT		intron	N/A	NP_001317272.1	Q9GZX7-2
	AICDA	NM_001410970.1		c.427+283_427+288delTTTTTT		intron	N/A	NP_001397899.1	Q6QJ80

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AICDA	ENST00000229335.11	TSL:1 MANE Select	c.428-10_428-5delTTTTTT		splice_region intron	N/A	ENSP00000229335.6	Q9GZX7-1
	AICDA	ENST00000543081.6	TSL:1	c.427+283_427+288delTTTTTT		intron	N/A	ENSP00000439103.2	Q6QJ80
	AICDA	ENST00000544516.6	TSL:1	c.157-595_157-590delTTTTTT		intron	N/A	ENSP00000439538.2	Q6QLN7

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 8.00e-7 AC: 1 AN: 1249680 Hom.: 0 AF XY: 0.00000161 AC XY: 1 AN XY: 622912

African (AFR) AF: 0.00 AC: 0 AN: 29126

American (AMR) AF: 0.00 AC: 0 AN: 33050

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22258

East Asian (EAS) AF: 0.00 AC: 0 AN: 33854

South Asian (SAS) AF: 0.00 AC: 0 AN: 73714

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43108

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3618

European-Non Finnish (NFE) AF: 0.00000104 AC: 1 AN: 959110

Other (OTH) AF: 0.00 AC: 0 AN: 51842

GnomAD4 genome Cov.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Hyper-IgM syndrome type 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.6

Splicing

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

Other links and lift over

dbSNP: rs5796316; hg19: chr12-8757522;