NM_001783.4:c.86_99delGGTGCCAGGCCCTG

Variant names:

• chr19-41878986-ACAGGCCCTGGGTGC-A
• NM_001783.4:c.86_99delGGTGCCAGGCCCTG

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PVS1_Strong PP5_Moderate

The NM_001783.4(CD79A):​c.86_99delGGTGCCAGGCCCTG​(p.Gly29fs) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. G29G) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CD79A NM_001783.4 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 5.02
• 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: Likely_pathogenic. The variant received 6 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.874 CDS is truncated, and there are 3 pathogenic variants in the truncated region.
• PP5: Variant 19-41878986-ACAGGCCCTGGGTGC-A is Pathogenic according to our data. Variant chr19-41878986-ACAGGCCCTGGGTGC-A is described in ClinVar as Pathogenic. ClinVar VariationId is 2128215.Status of the report is criteria_provided_single_submitter, 1 stars.

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.86_99delGGTGCCAGGCCCTG	p.Gly29fs	frameshift	Exon 2 of 5	NP_001774.1	P11912-1
	CD79A	NM_021601.4		c.86_99delGGTGCCAGGCCCTG	p.Gly29fs	frameshift	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.80-3_90delCAGGCCCTGGGTGC	p.Gly27fs	frameshift splice_acceptor splice_region intron	Exon 2 of 5	ENSP00000221972.3	P11912-1
	CD79A	ENST00000444740.2	TSL:1	c.80-3_90delCAGGCCCTGGGTGC	p.Gly27fs	frameshift splice_acceptor splice_region intron	Exon 2 of 5	ENSP00000400605.1	P11912-2
	CD79A	ENST00000597454.2	TSL:3	c.80-3_90delCAGGCCCTGGGTGC	p.Gly27fs	frameshift splice_acceptor splice_region intron	Exon 2 of 4	ENSP00000468922.2	M0QX61

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 911516 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 463704

African (AFR) AF: 0.00 AC: 0 AN: 21064

American (AMR) AF: 0.00 AC: 0 AN: 37870

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16224

East Asian (EAS) AF: 0.00 AC: 0 AN: 19192

South Asian (SAS) AF: 0.00 AC: 0 AN: 77256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30714

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4048

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 669840

Other (OTH) AF: 0.00 AC: 0 AN: 35308

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Pathogenic

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
PhyloP100		5.0

Splicing

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

Other links and lift over

hg19: chr19-42383056;