rs10406069

Variant names:

• chr19-35345627-G-A
• rs10406069
• NM_001771.4:c.2234G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 46 publications found

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: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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001771.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD22	NM_001771.4	MANE Select	c.2234G>A	p.Gly745Asp	missense	Exon 12 of 14	NP_001762.2	P20273-1
	CD22	NM_001185099.2		c.1970G>A	p.Gly657Asp	missense	Exon 11 of 13	NP_001172028.1	P20273-3
	CD22	NM_001278417.2		c.1718G>A	p.Gly573Asp	missense	Exon 11 of 13	NP_001265346.1	P20273-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD22	ENST00000085219.10	TSL:1 MANE Select	c.2234G>A	p.Gly745Asp	missense	Exon 12 of 14	ENSP00000085219.4	P20273-1
	CD22	ENST00000536635.6	TSL:1	c.1970G>A	p.Gly657Asp	missense	Exon 11 of 13	ENSP00000442279.1	P20273-3
	CD22	ENST00000419549.6	TSL:1	c.1718G>A	p.Gly573Asp	missense	Exon 11 of 13	ENSP00000403822.2	P20273-5

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

GnomAD2 exomes AF: 0.165 AC: 41386 AN: 251022 AF XY: 0.166

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 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

African (AFR) AF: 0.0602 AC: 2014 AN: 33430

American (AMR) AF: 0.0962 AC: 4296 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 4329 AN: 26078

East Asian (EAS) AF: 0.202 AC: 8029 AN: 39678

South Asian (SAS) AF: 0.0800 AC: 6895 AN: 86208

European-Finnish (FIN) AF: 0.182 AC: 9744 AN: 53404

Middle Eastern (MID) AF: 0.175 AC: 1009 AN: 5764

European-Non Finnish (NFE) AF: 0.203 AC: 224533 AN: 1107964

Other (OTH) AF: 0.181 AC: 10892 AN: 60218

GnomAD4 genome AF: 0.155 AC: 23467 AN: 151836 Hom.: 2179 Cov.: 30 AF XY: 0.153 AC XY: 11382 AN XY: 74184

African (AFR) AF: 0.0679 AC: 2811 AN: 41418

American (AMR) AF: 0.139 AC: 2121 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 586 AN: 3468

East Asian (EAS) AF: 0.231 AC: 1184 AN: 5120

South Asian (SAS) AF: 0.0853 AC: 411 AN: 4816

European-Finnish (FIN) AF: 0.181 AC: 1908 AN: 10542

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13725 AN: 67900

Other (OTH) AF: 0.159 AC: 335 AN: 2110

Alfa AF: 0.186 Hom.: 12777

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 v4.9

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
MetaRNN	Benign	0.0035	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		-0.11
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.013
Sift	Benign	0.17	T
Sift4G	Benign	0.29	T
Polyphen		0.082	B
Vest4		0.14
MPC		0.20
ClinPred		0.011	T
GERP RS		-1.4
Varity_R		0.16
gMVP		0.48
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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