rs34826052

Variant names:

• chr19-35345697-C-A
• rs34826052
• NM_001771.4:c.2304C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-35345697-C-A
• chr19-35345697-C-G
• chr19-35345697-C-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001771.4(CD22):​c.2304C>A​(p.Pro768Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.034 in 1,612,342 control chromosomes in the GnomAD database, including 1,451 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.030 (120 hom., cov: 31)
  • Exomes 𝑓: 0.035 (1331 hom.)
• Consequence: CD22 NM_001771.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.21
• Publications: 14 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP7: Synonymous conserved (PhyloP=-2.21 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.133 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD22	NM_001771.4	MANE Select	c.2304C>A	p.Pro768Pro	synonymous	Exon 12 of 14	NP_001762.2
	CD22	NM_001185099.2		c.2040C>A	p.Pro680Pro	synonymous	Exon 11 of 13	NP_001172028.1
	CD22	NM_001278417.2		c.1788C>A	p.Pro596Pro	synonymous	Exon 11 of 13	NP_001265346.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD22	ENST00000085219.10	TSL:1 MANE Select	c.2304C>A	p.Pro768Pro	synonymous	Exon 12 of 14	ENSP00000085219.4
	CD22	ENST00000536635.6	TSL:1	c.2040C>A	p.Pro680Pro	synonymous	Exon 11 of 13	ENSP00000442279.1
	CD22	ENST00000419549.6	TSL:1	c.1788C>A	p.Pro596Pro	synonymous	Exon 11 of 13	ENSP00000403822.2

Frequencies

GnomAD3 genomes AF: 0.0295 AC: 4492 AN: 152148 Hom.: 121 Cov.: 31

Gnomad AFR AF: 0.0196

Gnomad AMI AF: 0.00659

Gnomad AMR AF: 0.0172

Gnomad ASJ AF: 0.0179

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.0864

Gnomad FIN AF: 0.0265

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0275

Gnomad OTH AF: 0.0206

GnomAD2 exomes AF: 0.0398 AC: 9994 AN: 251328 AF XY: 0.0425

Gnomad AFR exome AF: 0.0189

Gnomad AMR exome AF: 0.0127

Gnomad ASJ exome AF: 0.0212

Gnomad EAS exome AF: 0.149

Gnomad FIN exome AF: 0.0253

Gnomad NFE exome AF: 0.0268

Gnomad OTH exome AF: 0.0287

GnomAD4 exome AF: 0.0345 AC: 50375 AN: 1460076 Hom.: 1331 Cov.: 31 AF XY: 0.0359 AC XY: 26115 AN XY: 726434

African (AFR) AF: 0.0180 AC: 601 AN: 33450

American (AMR) AF: 0.0124 AC: 553 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.0196 AC: 513 AN: 26126

East Asian (EAS) AF: 0.132 AC: 5257 AN: 39682

South Asian (SAS) AF: 0.0803 AC: 6918 AN: 86202

European-Finnish (FIN) AF: 0.0275 AC: 1471 AN: 53414

Middle Eastern (MID) AF: 0.0241 AC: 139 AN: 5762

European-Non Finnish (NFE) AF: 0.0295 AC: 32752 AN: 1110398

Other (OTH) AF: 0.0360 AC: 2171 AN: 60328

GnomAD4 genome AF: 0.0295 AC: 4497 AN: 152266 Hom.: 120 Cov.: 31 AF XY: 0.0316 AC XY: 2354 AN XY: 74434

African (AFR) AF: 0.0198 AC: 821 AN: 41552

American (AMR) AF: 0.0172 AC: 263 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0179 AC: 62 AN: 3472

East Asian (EAS) AF: 0.142 AC: 733 AN: 5178

South Asian (SAS) AF: 0.0862 AC: 416 AN: 4824

European-Finnish (FIN) AF: 0.0265 AC: 281 AN: 10614

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0275 AC: 1869 AN: 68008

Other (OTH) AF: 0.0204 AC: 43 AN: 2112

Alfa AF: 0.0269 Hom.: 177

Bravo AF: 0.0275

Asia WGS AF: 0.106 AC: 368 AN: 3478

EpiCase AF: 0.0271

EpiControl AF: 0.0269

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.038
DANN	Benign	0.75
PhyloP100		-2.2
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs34826052; hg19: chr19-35836600; COSMIC: COSV50050426; COSMIC: COSV50050426;