rs104894325

chr12-8605439-C-Achr12-8605439-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1 PM2 PP3

The NM_020661.4(AICDA):c.203G>T(p.Trp68Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: AICDA NM_020661.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.29

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 5 ACMG points.

• PM1: In a chain Single-stranded DNA cytosine deaminase (size 197) in uniprot entity AICDA_HUMAN there are 23 pathogenic changes around while only 3 benign (88%) in NM_020661.4
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.799

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AICDA	NM_020661.4	c.203G>T	p.Trp68Leu	missense_variant	3/5	ENST00000229335.11
AICDA	NM_001330343.2	c.203G>T	p.Trp68Leu	missense_variant	3/5
AICDA	NM_001410970.1	c.203G>T	p.Trp68Leu	missense_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AICDA	ENST00000229335.11	c.203G>T	p.Trp68Leu	missense_variant	3/5	1	NM_020661.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.070
Cadd	Pathogenic	27
Dann	Uncertain	0.99
DEOGEN2	Benign	0.37	T;.
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.035	D
MetaRNN	Pathogenic	0.80	D;D
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	1.2	L;L
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-10	D;D
REVEL	Uncertain	0.33
Sift	Benign	0.080	T;T
Sift4G	Benign	0.36	T;T
Polyphen		0.99	D;.
Vest4		0.66
MutPred		0.63		Gain of helix (P = 0.1736);Gain of helix (P = 0.1736);
MVP		0.90
MPC		2.5
ClinPred		1.0	D
GERP RS		5.4
Varity_R		0.94
gMVP		0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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: chr12-8758035;