Genetic Variant NM_001783.4:c.80G>A (chr19-41878990-G-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001783.4(CD79A):c.80G>A(p.Gly27Asp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,425,322 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CD79A
NM_001783.4 missense, splice_region

Scores

Splicing: ADA: 0.9977

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.83

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD79A	NM_001783.4 link	c.80G>A	p.Gly27Asp	missense_variant, splice_region_variant	Exon 2 of 5	ENST00000221972.8	NP_001774.1	P11912-1
CD79A	NM_021601.4 link	c.80G>A	p.Gly27Asp	missense_variant, splice_region_variant	Exon 2 of 5		NP_067612.1	P11912-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CD79A	ENST00000221972.8 link	c.80G>A	p.Gly27Asp	missense_variant, splice_region_variant	Exon 2 of 5	1	NM_001783.4	ENSP00000221972.3	P11912-1
CD79A	ENST00000444740.2 link	c.80G>A	p.Gly27Asp	missense_variant, splice_region_variant	Exon 2 of 5	1		ENSP00000400605.1	P11912-2
CD79A	ENST00000597454.2 link	c.80G>A	p.Gly27Asp	missense_variant, splice_region_variant	Exon 2 of 4	3		ENSP00000468922.2	M0QX61

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000140

AC:

AN:

1425322

Hom.:

Cov.:

AF XY:

0.00000282

AC XY:

AN XY:

709780

show subpopulations

Gnomad4 AFR exome

AF:

0.0000307

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:

9.17e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.030

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.53

D;T;.

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.70

T;T;T

M_CAP

Benign

0.042

MetaRNN

Pathogenic

0.75

D;D;D

MetaSVM

Uncertain

-0.055

MutationAssessor

Benign

1.0

L;.;L

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-3.0

D;.;D

REVEL

Uncertain

0.54

Sift

Benign

0.13

T;.;T

Sift4G

Uncertain

0.050

T;D;D

Polyphen

1.0

D;.;.

Vest4

0.47

MutPred

0.56

Loss of sheet (P = 0.0037);Loss of sheet (P = 0.0037);Loss of sheet (P = 0.0037);

MVP

0.73

MPC

1.5

ClinPred

0.97

GERP RS

4.5

Varity_R

0.23

gMVP

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.77

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over