19-41878990-G-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001783.4(CD79A):​c.80G>T​(p.Gly27Val) 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. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. G27G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CD79A NM_001783.4 missense, splice_region
• Scores: Splicing: ADA: 0.9997
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics
• autosomal agammaglobulinemia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001783.4. 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
	CD79A	NM_001783.4	MANE Select	c.80G>T	p.Gly27Val	missense splice_region	Exon 2 of 5	NP_001774.1	P11912-1
	CD79A	NM_021601.4		c.80G>T	p.Gly27Val	missense splice_region	Exon 2 of 5	NP_067612.1	P11912-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD79A	ENST00000221972.8	TSL:1 MANE Select	c.80G>T	p.Gly27Val	missense splice_region	Exon 2 of 5	ENSP00000221972.3	P11912-1
	CD79A	ENST00000444740.2	TSL:1	c.80G>T	p.Gly27Val	missense splice_region	Exon 2 of 5	ENSP00000400605.1	P11912-2
	CD79A	ENST00000597454.2	TSL:3	c.80G>T	p.Gly27Val	missense splice_region	Exon 2 of 4	ENSP00000468922.2	M0QX61

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Agammaglobulinemia 3, autosomal recessive (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.65	D
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.072	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Uncertain	-0.068	T
MutationAssessor	Benign	1.0	L
PhyloP100		1.8
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-4.4	D
REVEL	Uncertain	0.57
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.64
MutPred		0.55		Loss of sheet (P = 0.007)
MVP		0.85
MPC		1.4
ClinPred		0.99	D
GERP RS		4.5
Varity_R		0.50
gMVP		0.68
Mutation Taster		=76/24	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.91
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;