19-35346802-A-G

Variant names:

• chr19-35346802-A-G
• rs35529786
• NM_001771.4:c.*105A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001771.4(CD22):​c.*105A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 733,532 control chromosomes in the GnomAD database, including 19,763 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 0.20 (3156 hom., cov: 32)
  • Exomes 𝑓: 0.28 (16607 hom.)
• Consequence: CD22 NM_001771.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.139
• Publications: 6 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.225 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.*105A>G		3_prime_UTR	Exon 14 of 14	NP_001762.2
	CD22	NM_001185099.2		c.*105A>G		3_prime_UTR	Exon 13 of 13	NP_001172028.1
	CD22	NM_001185100.2		c.*274A>G		3_prime_UTR	Exon 13 of 13	NP_001172029.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD22	ENST00000085219.10	TSL:1 MANE Select	c.*105A>G		3_prime_UTR	Exon 14 of 14	ENSP00000085219.4
	CD22	ENST00000536635.6	TSL:1	c.*105A>G		3_prime_UTR	Exon 13 of 13	ENSP00000442279.1
	CD22	ENST00000544992.6	TSL:1	c.*274A>G		3_prime_UTR	Exon 13 of 13	ENSP00000441237.1

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30121 AN: 147580 Hom.: 3159 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.306

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.224

GnomAD4 exome AF: 0.280 AC: 164024 AN: 585866 Hom.: 16607 Cov.: 9 AF XY: 0.276 AC XY: 81838 AN XY: 296268

African (AFR) AF: 0.232 AC: 3205 AN: 13792

American (AMR) AF: 0.192 AC: 2908 AN: 15172

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 3347 AN: 11192

East Asian (EAS) AF: 0.188 AC: 3930 AN: 20850

South Asian (SAS) AF: 0.151 AC: 5694 AN: 37608

European-Finnish (FIN) AF: 0.250 AC: 6634 AN: 26514

Middle Eastern (MID) AF: 0.343 AC: 688 AN: 2004

European-Non Finnish (NFE) AF: 0.301 AC: 130142 AN: 431772

Other (OTH) AF: 0.277 AC: 7476 AN: 26962

GnomAD4 genome AF: 0.204 AC: 30114 AN: 147666 Hom.: 3156 Cov.: 32 AF XY: 0.201 AC XY: 14496 AN XY: 72166

African (AFR) AF: 0.187 AC: 7090 AN: 38012

American (AMR) AF: 0.183 AC: 2768 AN: 15122

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 763 AN: 3284

East Asian (EAS) AF: 0.181 AC: 920 AN: 5094

South Asian (SAS) AF: 0.101 AC: 480 AN: 4746

European-Finnish (FIN) AF: 0.179 AC: 1882 AN: 10488

Middle Eastern (MID) AF: 0.309 AC: 89 AN: 288

European-Non Finnish (NFE) AF: 0.228 AC: 15452 AN: 67666

Other (OTH) AF: 0.225 AC: 466 AN: 2068

Alfa AF: 0.197 Hom.: 303

Bravo AF: 0.198

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.72
DANN	Benign	0.58
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs35529786; hg19: chr19-35837705;