Genetic Variant CD22:p.Cys484Cys (chr19-35341083-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001771.4(CD22):c.1452C>T(p.Cys484Cys) 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.819

Publications

5 publications found

Variant links:

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]

CD22 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CD22	NM_001771.4 link	c.1452C>T	p.Cys484Cys	synonymous_variant	Exon 7 of 14	ENST00000085219.10	NP_001762.2	P20273-1Q0EAF5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD22	ENST00000085219.10 link	c.1452C>T	p.Cys484Cys	synonymous_variant	Exon 7 of 14	1	NM_001771.4	ENSP00000085219.4		P20273-1

Frequencies

GnomAD3 genomes

AF:

0.0542

AC:

8243

AN:

152110

Hom.:

562

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.0205

AC:

5164

AN:

251456

AF XY:

0.0172

show subpopulations

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 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.:

AF XY:

0.0138

AC XY:

10046

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.176

AC:

5893

AN:

33478

American (AMR)

AF:

0.0178

AC:

797

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0368

AC:

963

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00188

AC:

162

AN:

86258

European-Finnish (FIN)

AF:

0.00344

AC:

184

AN:

53420

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0105

AC:

11726

AN:

1112006

Other (OTH)

AF:

0.0212

AC:

1282

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

1249

2499

3748

4998

6247

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

528

1056

1584

2112

2640

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0545

AC:

8290

AN:

152228

Hom.:

572

Cov.:

AF XY:

0.0531

AC XY:

3949

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.164

AC:

6791

AN:

41504

American (AMR)

AF:

0.0313

AC:

479

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0377

AC:

131

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00166

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00132

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0111

AC:

752

AN:

68024

Other (OTH)

AF:

0.0464

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

367

734

1101

1468

1835

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

252

336

420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0290

Hom.:

124

Bravo

AF:

0.0615

Asia WGS

AF:

0.0120

AC:

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

(source)

DANN

Benign

0.76

PhyloP100

-0.82

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over