Genetic Variant CD22:c.*246C>T (chr19-35346943-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001771.4(CD22):c.*246C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0167 in 445,036 control chromosomes in the GnomAD database, including 142 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 0.026 ( 108 hom., cov: 32)

Exomes 𝑓: 0.012 ( 34 hom. )

Consequence

CD22
NM_001771.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.23

Publications

2 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0632 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001771.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CD22	NM_001771.4	MANE Select	c.*246C>T	3_prime_UTR	Exon 14 of 14	NP_001762.2
CD22	NM_001185099.2		c.*246C>T	3_prime_UTR	Exon 13 of 13	NP_001172028.1
CD22	NM_001185100.2		c.*415C>T	3_prime_UTR	Exon 13 of 13	NP_001172029.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CD22	ENST00000085219.10	TSL:1 MANE Select	c.*246C>T	3_prime_UTR	Exon 14 of 14	ENSP00000085219.4
CD22	ENST00000536635.6	TSL:1	c.*246C>T	3_prime_UTR	Exon 13 of 13	ENSP00000442279.1
CD22	ENST00000918678.1		c.*246C>T	3_prime_UTR	Exon 15 of 15	ENSP00000588737.1

Frequencies

GnomAD3 genomes

AF:

0.0262

AC:

3983

AN:

152128

Hom.:

108

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0653

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.0161

Gnomad ASJ

AF:

0.0233

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00480

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0121

Gnomad OTH

AF:

0.0278

GnomAD4 exome

AF:

0.0118

AC:

3443

AN:

292790

Hom.:

Cov.:

AF XY:

0.0114

AC XY:

1747

AN XY:

153262

show subpopulations

African (AFR)

AF:

0.0592

AC:

429

AN:

7248

American (AMR)

AF:

0.0117

AC:

105

AN:

8994

Ashkenazi Jewish (ASJ)

AF:

0.0230

AC:

215

AN:

9350

East Asian (EAS)

AF:

0.0000539

AC:

AN:

18558

South Asian (SAS)

AF:

0.00184

AC:

AN:

28304

European-Finnish (FIN)

AF:

0.00556

AC:

106

AN:

19068

Middle Eastern (MID)

AF:

0.00954

AC:

AN:

1362

European-Non Finnish (NFE)

AF:

0.0123

AC:

2251

AN:

182388

Other (OTH)

AF:

0.0155

AC:

271

AN:

17518

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

162

325

487

650

812

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.0262

AC:

3990

AN:

152246

Hom.:

108

Cov.:

AF XY:

0.0251

AC XY:

1871

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.0653

AC:

2711

AN:

41540

American (AMR)

AF:

0.0160

AC:

244

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0233

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00186

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00480

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0121

AC:

824

AN:

68014

Other (OTH)

AF:

0.0275

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

180

360

541

721

901

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

176

220

<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:

0.0221

Hom.:

Bravo

AF:

0.0284

Asia WGS

AF:

0.00462

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.0

(source)

DANN

Benign

0.54

PhyloP100

-1.2

Mutation Taster

=100/0

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over