19-35346802-A-G

Position:

• chr19-35346802-A-G

Variant summary

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

The NM_001771.4(CD22):​c.*105A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 733,532 control chromosomes in the GnomAD database, including 19,763 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 0.20 (3156 hom., cov: 32)
  • Exomes 𝑓: 0.28 (16607 hom.)
• Consequence: CD22 NM_001771.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.139

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD22	NM_001771.4	c.*105A>G		3_prime_UTR_variant	14/14	ENST00000085219.10	NP_001762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD22	ENST00000085219.10	c.*105A>G		3_prime_UTR_variant	14/14	1	NM_001771.4	ENSP00000085219.4

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30121 AN: 147580 Hom.: 3159 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.306

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.224

GnomAD4 exome AF: 0.280 AC: 164024 AN: 585866 Hom.: 16607 Cov.: 9 AF XY: 0.276 AC XY: 81838 AN XY: 296268

Gnomad4 AFR exome AF: 0.232

Gnomad4 AMR exome AF: 0.192

Gnomad4 ASJ exome AF: 0.299

Gnomad4 EAS exome AF: 0.188

Gnomad4 SAS exome AF: 0.151

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.301

Gnomad4 OTH exome AF: 0.277

GnomAD4 genome AF: 0.204 AC: 30114 AN: 147666 Hom.: 3156 Cov.: 32 AF XY: 0.201 AC XY: 14496 AN XY: 72166

Gnomad4 AFR AF: 0.187

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.232

Gnomad4 EAS AF: 0.181

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.228

Gnomad4 OTH AF: 0.225

Alfa AF: 0.197 Hom.: 303

Bravo AF: 0.198

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.72
DANN	Benign	0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs35529786; hg19: chr19-35837705;