19-35341083-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.1452C>T(p.Cys484=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0182 in 1,614,114 control chromosomes in the GnomAD database, including 1,206 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 0.054 (572 hom., cov: 31)
  • Exomes 𝑓: 0.014 (634 hom.)
• Consequence: CD22 NM_001771.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.819

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=-0.75).
• BP7: Synonymous conserved (PhyloP=-0.819 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD22	NM_001771.4	c.1452C>T	p.Cys484=	synonymous_variant	7/14	ENST00000085219.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD22	ENST00000085219.10	c.1452C>T	p.Cys484=	synonymous_variant	7/14	1	NM_001771.4	P2

Frequencies

GnomAD3 genomes AF: 0.0542 AC: 8243 AN: 152110 Hom.: 562 Cov.: 31

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0314

Gnomad ASJ AF: 0.0377

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0111

Gnomad OTH AF: 0.0469

GnomAD3 exomes AF: 0.0205 AC: 5164 AN: 251456 Hom.: 266 AF XY: 0.0172 AC XY: 2333 AN XY: 135910

Gnomad AFR exome AF: 0.168

Gnomad AMR exome AF: 0.0166

Gnomad ASJ exome AF: 0.0366

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00176

Gnomad FIN exome AF: 0.00323

Gnomad NFE exome AF: 0.0109

Gnomad OTH exome AF: 0.0197

GnomAD4 exome AF: 0.0144 AC: 21106 AN: 1461886 Hom.: 634 Cov.: 33 AF XY: 0.0138 AC XY: 10046 AN XY: 727244

Gnomad4 AFR exome AF: 0.176

Gnomad4 AMR exome AF: 0.0178

Gnomad4 ASJ exome AF: 0.0368

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00188

Gnomad4 FIN exome AF: 0.00344

Gnomad4 NFE exome AF: 0.0105

Gnomad4 OTH exome AF: 0.0212

GnomAD4 genome AF: 0.0545 AC: 8290 AN: 152228 Hom.: 572 Cov.: 31 AF XY: 0.0531 AC XY: 3949 AN XY: 74438

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.0313

Gnomad4 ASJ AF: 0.0377

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.00132

Gnomad4 NFE AF: 0.0111

Gnomad4 OTH AF: 0.0464

Alfa AF: 0.0290 Hom.: 124

Bravo AF: 0.0615

Asia WGS AF: 0.0120 AC: 43 AN: 3478

EpiCase AF: 0.0110

EpiControl AF: 0.0119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	0.76
Dann	Benign	0.76

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: rs25677; hg19: chr19-35831986;