rs10406069

Positions:

• chr19-35345627-G-A
• chr19-35345627-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.15 (2179 hom., cov: 30)
  • Exomes 𝑓: 0.19 (26904 hom.)
• Consequence: CD22 NM_001771.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.111

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]

MIR5196 (HGNC:):

ACMG classification

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/exons	MANE	Protein	UniProt
CD22	NM_001771.4	c.2234G>A	p.Gly745Asp	missense_variant	12/14	ENST00000085219.10	NP_001762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD22	ENST00000085219.10	c.2234G>A	p.Gly745Asp	missense_variant	12/14	1	NM_001771.4	ENSP00000085219.4

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23478 AN: 151720 Hom.: 2180 Cov.: 30

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

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.: 31 AF XY: 0.184 AC XY: 133250 AN XY: 725332

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.: 30 AF XY: 0.153 AC XY: 11382 AN XY: 74184

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	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	10
DANN	Benign	0.70
DEOGEN2	Benign	0.34	.;.;T;.;.
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.57	T;T;T;T;.
MetaRNN	Benign	0.0035	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	.;.;L;.;.
PrimateAI	Benign	0.32	T
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	T
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

Other links and lift over

dbSNP: rs10406069; hg19: chr19-35836530; COSMIC: COSV50050834; COSMIC: COSV50050834;