chr19-41878986-ACAGGCCCTGGGTGC-A

Position:

• chr19-41878986-ACAGGCCCTGGGTGC-A

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_Strong PM2 PP5_Moderate

The NM_001783.4(CD79A):​c.86_99del​(p.Gly29ValfsTer25) variant causes a splice acceptor, coding sequence, intron change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CD79A NM_001783.4 splice_acceptor, coding_sequence, intron
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 5.02

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.4390602 fraction of the gene. Cryptic splice site detected, with MaxEntScore 14, offset of 0 (no position change), new splice context is: cccaccctgtctctccacAGgcc. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in inframe change.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 19-41878986-ACAGGCCCTGGGTGC-A is Pathogenic according to our data. Variant chr19-41878986-ACAGGCCCTGGGTGC-A is described in ClinVar as [Pathogenic]. Clinvar id is 2128215.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD79A	NM_001783.4	c.86_99del	p.Gly29ValfsTer25	splice_acceptor_variant, coding_sequence_variant, intron_variant	2/5	ENST00000221972.8
CD79A	NM_021601.4	c.86_99del	p.Gly29ValfsTer25	splice_acceptor_variant, coding_sequence_variant, intron_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD79A	ENST00000221972.8	c.86_99del	p.Gly29ValfsTer25	splice_acceptor_variant, coding_sequence_variant, intron_variant	2/5	1	NM_001783.4	P1
CD79A	ENST00000444740.2	c.86_99del	p.Gly29ValfsTer25	splice_acceptor_variant, coding_sequence_variant, intron_variant	2/5	1
CD79A	ENST00000597454.2	c.86_99del	p.Gly29ValfsTer25	splice_acceptor_variant, coding_sequence_variant, intron_variant	2/4	3

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Agammaglobulinemia 3, autosomal recessive Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 20, 2022

This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CD79A-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Gly29Valfs*25) in the CD79A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CD79A are known to be pathogenic (PMID: 10525050, 24481606). -

Computational scores

Source: dbNSFP v4.3

Splicing

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: chr19-42383056;