19-35345867-G-A

Position:

• chr19-35345867-G-A

Variant summary

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

The NM_001771.4(CD22):​c.2327+147G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 685,932 control chromosomes in the GnomAD database, including 10,246 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 0.16 (2263 hom., cov: 32)
  • Exomes 𝑓: 0.16 (7983 hom.)
• Consequence: CD22 NM_001771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.71

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD22	NM_001771.4	c.2327+147G>A		intron_variant		ENST00000085219.10	NP_001762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD22	ENST00000085219.10	c.2327+147G>A		intron_variant		1	NM_001771.4	ENSP00000085219	P2

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24890 AN: 152104 Hom.: 2254 Cov.: 32

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.0570

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.165

GnomAD4 exome AF: 0.158 AC: 84498 AN: 533710 Hom.: 7983 AF XY: 0.167 AC XY: 47501 AN XY: 284754

Gnomad4 AFR exome AF: 0.215

Gnomad4 AMR exome AF: 0.227

Gnomad4 ASJ exome AF: 0.205

Gnomad4 EAS exome AF: 0.0842

Gnomad4 SAS exome AF: 0.322

Gnomad4 FIN exome AF: 0.121

Gnomad4 NFE exome AF: 0.132

Gnomad4 OTH exome AF: 0.159

GnomAD4 genome AF: 0.164 AC: 24929 AN: 152222 Hom.: 2263 Cov.: 32 AF XY: 0.166 AC XY: 12354 AN XY: 74440

Gnomad4 AFR AF: 0.212

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.0573

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.120

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.165

Alfa AF: 0.146 Hom.: 1678

Bravo AF: 0.167

Asia WGS AF: 0.206 AC: 716 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.6
DANN	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs10406539; hg19: chr19-35836770;