19-41878986-ACAGGCCCTGGGTGC-A

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 ENST00000221972.8(CD79A):​c.80-3_90delCAGGCCCTGGGTGC​(p.Gly27fs) variant causes a frameshift, splice acceptor, splice region, intron 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. G27G) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CD79A ENST00000221972.8 frameshift, splice_acceptor, splice_region, intron
• 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 0.883 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: ENST00000221972.8. 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;