19-41878990-G-C

Variant names:

• chr19-41878990-G-C
• rs2074204427
• NM_001783.4:c.80G>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001783.4(CD79A):​c.80G>C​(p.Gly27Ala) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G27V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CD79A NM_001783.4 missense, splice_region
• Scores: Splicing: ADA: 0.9998
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.83
• Publications: 0 publications found

Genes affected

CD79A (HGNC:1698): (CD79a molecule) The B lymphocyte antigen receptor is a multimeric complex that includes the antigen-specific component, surface immunoglobulin (Ig). Surface Ig non-covalently associates with two other proteins, Ig-alpha and Ig-beta, which are necessary for expression and function of the B-cell antigen receptor. This gene encodes the Ig-alpha protein of the B-cell antigen component. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

CD79A Gene-Disease associations (from GenCC):

• agammaglobulinemia 3, autosomal recessive

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen
• autosomal agammaglobulinemia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD79A	NM_001783.4	c.80G>C	p.Gly27Ala	missense_variant, splice_region_variant	Exon 2 of 5	ENST00000221972.8	NP_001774.1
CD79A	NM_021601.4	c.80G>C	p.Gly27Ala	missense_variant, splice_region_variant	Exon 2 of 5		NP_067612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD79A	ENST00000221972.8	c.80G>C	p.Gly27Ala	missense_variant, splice_region_variant	Exon 2 of 5	1	NM_001783.4	ENSP00000221972.3
CD79A	ENST00000444740.2	c.80G>C	p.Gly27Ala	missense_variant, splice_region_variant	Exon 2 of 5	1		ENSP00000400605.1
CD79A	ENST00000597454.2	c.80G>C	p.Gly27Ala	missense_variant, splice_region_variant	Exon 2 of 4	3		ENSP00000468922.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.035	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.42	T;T;.
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.75	T;T;T
M_CAP	Benign	0.058	D
MetaRNN	Uncertain	0.61	D;D;D
MetaSVM	Uncertain	-0.17	T
MutationAssessor	Benign	1.0	L;.;L
PhyloP100		1.8
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.9	D;.;D
REVEL	Uncertain	0.44
Sift	Uncertain	0.011	D;.;D
Sift4G	Uncertain	0.022	D;D;D
Polyphen		0.99	D;.;.
Vest4		0.38
MutPred		0.57		Loss of sheet (P = 0.007);Loss of sheet (P = 0.007);Loss of sheet (P = 0.007);
MVP		0.68
MPC		1.3
ClinPred		0.93	D
GERP RS		4.5
Varity_R		0.22
gMVP		0.63
Mutation Taster		=77/23	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.88
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

Other links and lift over

dbSNP: rs2074204427; hg19: chr19-42383060;