Variant 19-35337928-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001771.4(CD22):c.892G>A(p.Glu298Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0025 in 1,614,228 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0013 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0026 ( 8 hom. )

Consequence

CD22
NM_001771.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -4.01

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 made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008769512).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD22	NM_001771.4 linkuse as main transcript	c.892G>A	p.Glu298Lys	missense_variant	5/14	ENST00000085219.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD22	ENST00000085219.10 linkuse as main transcript	c.892G>A	p.Glu298Lys	missense_variant	5/14	1	NM_001771.4	P2	P20273-1

Frequencies

GnomAD3 genomes

AF:

0.00129

AC:

197

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00245

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00151

AC:

379

AN:

251378

Hom.:

AF XY:

0.00136

AC XY:

185

AN XY:

135858

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.00298

Gnomad ASJ exome

AF:

0.000794

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00219

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.00262

AC:

3834

AN:

1461874

Hom.:

Cov.:

AF XY:

0.00253

AC XY:

1843

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.00253

Gnomad4 ASJ exome

AF:

0.000650

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.000225

Gnomad4 NFE exome

AF:

0.00310

Gnomad4 OTH exome

AF:

0.00381

GnomAD4 genome

AF:

0.00129

AC:

197

AN:

152354

Hom.:

Cov.:

AF XY:

0.000966

AC XY:

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00245

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00213

Hom.:

Bravo

AF:

0.00154

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.00285

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00279

AC:

ExAC

AF:

0.00140

AC:

170

EpiCase

AF:

0.00267

EpiControl

AF:

0.00166

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago

Mar 30, 2021

CD22 NM_001771.3 exon 5 p.Glu298Lys (c.892G>A): This variant has not been reported in the literature but is present in 0.2% (104/35422) of Latino alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/19-35828831-G-A?dataset=gnomad_r2_1). This variant amino acid Lysine (Lys) is present in >10 species including mammals and is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.71

Cadd

Benign

0.0010

Dann

Benign

0.65

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.58

T;T;T;T

M_CAP

Benign

0.0028

MetaRNN

Benign

0.0088

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.045

N;N;N;.

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.52

N;N;N;N

REVEL

Benign

0.035

Sift

Benign

0.96

T;T;T;T

Sift4G

Benign

0.86

T;T;T;T

Polyphen

0.13

.;B;.;.

Vest4

0.17

MVP

0.18

MPC

0.15

ClinPred

0.012

GERP RS

-10

Varity_R

0.077

gMVP

0.60

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

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