rs12985354

Positions:

• chr19-35346525-G-A
• chr19-35346525-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000085219.10(CD22):​c.2413-41G>A variant causes a intron change. The variant allele was found at a frequency of 0.301 in 1,573,200 control chromosomes in the GnomAD database, including 73,023 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 0.32 (8387 hom., cov: 32)
  • Exomes 𝑓: 0.30 (64636 hom.)
• Consequence: CD22 ENST00000085219.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.83

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD22	NM_001771.4	c.2413-41G>A		intron_variant		ENST00000085219.10	NP_001762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD22	ENST00000085219.10	c.2413-41G>A		intron_variant		1	NM_001771.4	ENSP00000085219	P2

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49185 AN: 152012 Hom.: 8362 Cov.: 32

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.332

GnomAD3 exomes AF: 0.281 AC: 52619 AN: 187230 Hom.: 7672 AF XY: 0.278 AC XY: 27913 AN XY: 100412

Gnomad AFR exome AF: 0.404

Gnomad AMR exome AF: 0.230

Gnomad ASJ exome AF: 0.318

Gnomad EAS exome AF: 0.224

Gnomad SAS exome AF: 0.219

Gnomad FIN exome AF: 0.264

Gnomad NFE exome AF: 0.313

Gnomad OTH exome AF: 0.293

GnomAD4 exome AF: 0.299 AC: 424775 AN: 1421070 Hom.: 64636 Cov.: 34 AF XY: 0.296 AC XY: 208324 AN XY: 703366

Gnomad4 AFR exome AF: 0.407

Gnomad4 AMR exome AF: 0.236

Gnomad4 ASJ exome AF: 0.320

Gnomad4 EAS exome AF: 0.185

Gnomad4 SAS exome AF: 0.225

Gnomad4 FIN exome AF: 0.270

Gnomad4 NFE exome AF: 0.308

Gnomad4 OTH exome AF: 0.301

GnomAD4 genome AF: 0.324 AC: 49254 AN: 152130 Hom.: 8387 Cov.: 32 AF XY: 0.318 AC XY: 23680 AN XY: 74364

Gnomad4 AFR AF: 0.400

Gnomad4 AMR AF: 0.269

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.219

Gnomad4 SAS AF: 0.213

Gnomad4 FIN AF: 0.265

Gnomad4 NFE AF: 0.315

Gnomad4 OTH AF: 0.332

Alfa AF: 0.308 Hom.: 10245

Bravo AF: 0.328

Asia WGS AF: 0.227 AC: 791 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	15
DANN	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs12985354; hg19: chr19-35837428; COSMIC: COSV50051923; COSMIC: COSV50051923;