dbSNP rs10406069: CD22:p.Gly745Asp (chr19-35345627-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001771.4(CD22):c.2234G>A(p.Gly745Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 1,609,258 control chromosomes in the GnomAD database, including 29,083 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.15 ( 2179 hom., cov: 30)

Exomes 𝑓: 0.19 ( 26904 hom. )

Consequence

CD22
NM_001771.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.111

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:

MIR5196 (HGNC:43542): (microRNA 5196) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR5196 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0034743845).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD22	NM_001771.4 link	c.2234G>A	p.Gly745Asp	missense_variant	Exon 12 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.2234G>A	p.Gly745Asp	missense_variant	Exon 12 of 14	1	NM_001771.4	ENSP00000085219.4		P20273-1

Frequencies

GnomAD3 genomes

AF:

0.155

AC:

23478

AN:

151720

Hom.:

2180

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0681

Gnomad AMI

AF:

0.374

Gnomad AMR

AF:

0.139

Gnomad ASJ

AF:

0.169

Gnomad EAS

AF:

0.231

Gnomad SAS

AF:

0.0856

Gnomad FIN

AF:

0.181

Gnomad MID

AF:

0.168

Gnomad NFE

AF:

0.202

Gnomad OTH

AF:

0.158

GnomAD3 exomes

AF:

0.165

AC:

41386

AN:

251022

Hom.:

3900

AF XY:

0.166

AC XY:

22501

AN XY:

135702

show subpopulations

Gnomad AFR exome

AF:

0.0653

Gnomad AMR exome

AF:

0.0910

Gnomad ASJ exome

AF:

0.172

Gnomad EAS exome

AF:

0.236

Gnomad SAS exome

AF:

0.0760

Gnomad FIN exome

AF:

0.182

Gnomad NFE exome

AF:

0.210

Gnomad OTH exome

AF:

0.173

GnomAD4 exome

AF:

0.186

AC:

271741

AN:

1457422

Hom.:

26904

Cov.:

AF XY:

0.184

AC XY:

133250

AN XY:

725332

show subpopulations

Gnomad4 AFR exome

AF:

0.0602

Gnomad4 AMR exome

AF:

0.0962

Gnomad4 ASJ exome

AF:

0.166

Gnomad4 EAS exome

AF:

0.202

Gnomad4 SAS exome

AF:

0.0800

Gnomad4 FIN exome

AF:

0.182

Gnomad4 NFE exome

AF:

0.203

Gnomad4 OTH exome

AF:

0.181

GnomAD4 genome

AF:

0.155

AC:

23467

AN:

151836

Hom.:

2179

Cov.:

AF XY:

0.153

AC XY:

11382

AN XY:

74184

show subpopulations

Gnomad4 AFR

AF:

0.0679

Gnomad4 AMR

AF:

0.139

Gnomad4 ASJ

AF:

0.169

Gnomad4 EAS

AF:

0.231

Gnomad4 SAS

AF:

0.0853

Gnomad4 FIN

AF:

0.181

Gnomad4 NFE

AF:

0.202

Gnomad4 OTH

AF:

0.159

Alfa

AF:

0.189

Hom.:

6640

Bravo

AF:

0.149

TwinsUK

AF:

0.198

AC:

733

ALSPAC

AF:

0.195

AC:

751

ESP6500AA

AF:

0.0713

AC:

314

ESP6500EA

AF:

0.207

AC:

1781

ExAC

AF:

0.170

AC:

20589

Asia WGS

AF:

0.149

AC:

519

AN:

3478

EpiCase

AF:

0.201

EpiControl

AF:

0.202

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.70

DEOGEN2

Benign

0.34

.;.;T;.;.

Eigen

Benign

-0.99

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.57

T;T;T;T;.

MetaRNN

Benign

0.0035

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

.;.;L;.;.

PrimateAI

Benign

0.32

PROVEAN

Uncertain

-3.0

D;D;D;D;.

REVEL

Benign

0.013

Sift

Benign

0.17

T;T;T;T;.

Sift4G

Benign

0.29

T;T;T;T;T

Polyphen

0.082

B;.;B;.;B

Vest4

0.14

MPC

0.20

ClinPred

0.011

GERP RS

-1.4

Varity_R

0.16

gMVP

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over