19-41880942-A-T

Variant names:

• chr19-41880942-A-T
• rs550589218
• NM_001783.4:c.643A>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001783.4(CD79A):​c.643A>T​(p.Ser215Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000000692 in 1,444,500 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. S215G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CD79A NM_001783.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.87
• Publications: 1 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30243027).

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.643A>T	p.Ser215Cys	missense	Exon 5 of 5	NP_001774.1	P11912-1
	CD79A	NM_021601.4		c.529A>T	p.Ser177Cys	missense	Exon 5 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.643A>T	p.Ser215Cys	missense	Exon 5 of 5	ENSP00000221972.3	P11912-1
	CD79A	ENST00000444740.2	TSL:1	c.529A>T	p.Ser177Cys	missense	Exon 5 of 5	ENSP00000400605.1	P11912-2
	CD79A	ENST00000597454.2	TSL:3	c.*69A>T		3_prime_UTR	Exon 4 of 4	ENSP00000468922.2	M0QX61

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000919 AC: 2 AN: 217590 AF XY: 0.00000852

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000324

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000102

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1444500 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 716742

African (AFR) AF: 0.00 AC: 0 AN: 33390

American (AMR) AF: 0.0000238 AC: 1 AN: 42020

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25602

East Asian (EAS) AF: 0.00 AC: 0 AN: 39160

South Asian (SAS) AF: 0.00 AC: 0 AN: 83030

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50998

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1104766

Other (OTH) AF: 0.00 AC: 0 AN: 59786

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.052	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.52	D
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.082	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.42	T
MutationAssessor	Benign	0.34	N
PhyloP100		4.9
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	-2.3	N
REVEL	Uncertain	0.33
Sift	Benign	0.12	T
Sift4G	Benign	0.18	T
Polyphen		1.0	D
Vest4		0.33
MutPred		0.41		Loss of disorder (P = 0.0402)
MVP		0.69
MPC		1.2
ClinPred		0.70	D
GERP RS		3.5
Varity_R		0.12
gMVP		0.54
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs550589218; hg19: chr19-42385009;