Variant chr19-35336229-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001771.4(CD22):c.606C>A(p.Ser202Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

CD22
NM_001771.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.48

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 made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.94

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD22	NM_001771.4 link	c.606C>A	p.Ser202Arg	missense_variant	4/14	ENST00000085219.10	NP_001762.2	P20273-1Q0EAF5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD22	ENST00000085219.10 link	c.606C>A	p.Ser202Arg	missense_variant	4/14	1	NM_001771.4	ENSP00000085219.4		P20273-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000358

AC:

AN:

251458

Hom.:

AF XY:

0.0000515

AC XY:

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000192

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.0000261

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000278

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 07, 2024

The c.606C>A (p.S202R) alteration is located in exon 4 (coding exon 3) of the CD22 gene. This alteration results from a C to A substitution at nucleotide position 606, causing the serine (S) at amino acid position 202 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.84

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Pathogenic

0.21

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.86

.;D;.;D;.;.;.;.

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.78

T;T;T;T;T;T;.;T

M_CAP

Benign

0.055

MetaRNN

Pathogenic

0.94

D;D;D;D;D;D;D;D

MetaSVM

Uncertain

0.012

MutationAssessor

Pathogenic

3.1

M;.;M;M;M;.;M;.

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-3.6

D;.;D;D;D;D;.;.

REVEL

Uncertain

0.64

Sift

Benign

0.33

T;.;T;D;D;D;.;.

Sift4G

Uncertain

0.0030

D;D;D;D;D;D;D;D

Polyphen

0.020

B;.;.;D;.;.;B;.

Vest4

0.77

MutPred

0.81

Gain of MoRF binding (P = 0.0371);Gain of MoRF binding (P = 0.0371);Gain of MoRF binding (P = 0.0371);Gain of MoRF binding (P = 0.0371);Gain of MoRF binding (P = 0.0371);.;Gain of MoRF binding (P = 0.0371);.;

MVP

0.81

MPC

0.52

ClinPred

0.71

GERP RS

3.5

Varity_R

0.99

gMVP

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over