Variant 19-35332053-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001771.4(CD22):c.13G>A(p.Gly5Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000973 in 1,613,754 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000086 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000099 ( 1 hom. )

Consequence

CD22
NM_001771.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.145

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.022943616).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD22	NM_001771.4 linkuse as main transcript	c.13G>A	p.Gly5Ser	missense_variant	2/14	ENST00000085219.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD22	ENST00000085219.10 linkuse as main transcript	c.13G>A	p.Gly5Ser	missense_variant	2/14	1	NM_001771.4	P2	P20273-1

Frequencies

GnomAD3 genomes

AF:

0.0000855

AC:

AN:

152022

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00187

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000159

AC:

AN:

251468

Hom.:

AF XY:

0.000243

AC XY:

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00118

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.0000985

AC:

144

AN:

1461732

Hom.:

Cov.:

AF XY:

0.000140

AC XY:

102

AN XY:

727162

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00139

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000719

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.0000855

AC:

AN:

152022

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74258

show subpopulations

Gnomad4 AFR

AF:

0.0000725

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00187

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000422

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.000181

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

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

Jun 11, 2021

The c.13G>A (p.G5S) alteration is located in exon 2 (coding exon 1) of the CD22 gene. This alteration results from a G to A substitution at nucleotide position 13, causing the glycine (G) at amino acid position 5 to be replaced by a serine (S). 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

Benign

0.15

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.50

CADD

Benign

8.4

DANN

Benign

0.87

DEOGEN2

Benign

0.26

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

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.081

LIST_S2

Benign

0.70

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

M_CAP

Benign

0.0062

MetaRNN

Benign

0.023

T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Benign

0.31

Sift4G

Benign

0.17

T;T;T;T;T;T;T;T;T;T;T;T

Polyphen

0.39, 0.27

.;B;.;.;.;.;.;.;.;B;.;B

Vest4

0.18, 0.18, 0.17, 0.12, 0.19

MutPred

0.48

Gain of disorder (P = 0.0732);Gain of disorder (P = 0.0732);Gain of disorder (P = 0.0732);Gain of disorder (P = 0.0732);Gain of disorder (P = 0.0732);Gain of disorder (P = 0.0732);Gain of disorder (P = 0.0732);Gain of disorder (P = 0.0732);Gain of disorder (P = 0.0732);Gain of disorder (P = 0.0732);Gain of disorder (P = 0.0732);Gain of disorder (P = 0.0732);

MVP

0.39

MPC

0.13

ClinPred

0.032

GERP RS

-4.6

Varity_R

0.10

gMVP

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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