rs34826052

Positions:

• chr19-35345697-C-A
• chr19-35345697-C-G
• chr19-35345697-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001771.4(CD22):​c.2304C>A​(p.Pro768Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.034 in 1,612,342 control chromosomes in the GnomAD database, including 1,451 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.030 (120 hom., cov: 31)
  • Exomes 𝑓: 0.035 (1331 hom.)
• Consequence: CD22 NM_001771.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.21

Genes affected

CD22 (HGNC:1643): (CD22 molecule) Predicted to enable CD4 receptor binding activity; protein phosphatase binding activity; and sialic acid binding activity. Involved in B cell activation; negative regulation of B cell receptor signaling pathway; and regulation of endocytosis. Located in early endosome and recycling endosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP7: Synonymous conserved (PhyloP=-2.21 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD22	NM_001771.4	c.2304C>A	p.Pro768Pro	synonymous_variant	12/14	ENST00000085219.10	NP_001762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD22	ENST00000085219.10	c.2304C>A	p.Pro768Pro	synonymous_variant	12/14	1	NM_001771.4	ENSP00000085219.4

Frequencies

GnomAD3 genomes AF: 0.0295 AC: 4492 AN: 152148 Hom.: 121 Cov.: 31

Gnomad AFR AF: 0.0196

Gnomad AMI AF: 0.00659

Gnomad AMR AF: 0.0172

Gnomad ASJ AF: 0.0179

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.0864

Gnomad FIN AF: 0.0265

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0275

Gnomad OTH AF: 0.0206

GnomAD3 exomes AF: 0.0398 AC: 9994 AN: 251328 Hom.: 414 AF XY: 0.0425 AC XY: 5769 AN XY: 135830

Gnomad AFR exome AF: 0.0189

Gnomad AMR exome AF: 0.0127

Gnomad ASJ exome AF: 0.0212

Gnomad EAS exome AF: 0.149

Gnomad SAS exome AF: 0.0822

Gnomad FIN exome AF: 0.0253

Gnomad NFE exome AF: 0.0268

Gnomad OTH exome AF: 0.0287

GnomAD4 exome AF: 0.0345 AC: 50375 AN: 1460076 Hom.: 1331 Cov.: 31 AF XY: 0.0359 AC XY: 26115 AN XY: 726434

Gnomad4 AFR exome AF: 0.0180

Gnomad4 AMR exome AF: 0.0124

Gnomad4 ASJ exome AF: 0.0196

Gnomad4 EAS exome AF: 0.132

Gnomad4 SAS exome AF: 0.0803

Gnomad4 FIN exome AF: 0.0275

Gnomad4 NFE exome AF: 0.0295

Gnomad4 OTH exome AF: 0.0360

GnomAD4 genome AF: 0.0295 AC: 4497 AN: 152266 Hom.: 120 Cov.: 31 AF XY: 0.0316 AC XY: 2354 AN XY: 74434

Gnomad4 AFR AF: 0.0198

Gnomad4 AMR AF: 0.0172

Gnomad4 ASJ AF: 0.0179

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.0862

Gnomad4 FIN AF: 0.0265

Gnomad4 NFE AF: 0.0275

Gnomad4 OTH AF: 0.0204

Alfa AF: 0.0229 Hom.: 39

Bravo AF: 0.0275

Asia WGS AF: 0.106 AC: 368 AN: 3478

EpiCase AF: 0.0271

EpiControl AF: 0.0269

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.038
DANN	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs34826052; hg19: chr19-35836600; COSMIC: COSV50050426; COSMIC: COSV50050426;