19-35346424-C-T

Position:

• chr19-35346424-C-T

Variant summary

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

The NM_001771.4(CD22):​c.2413-142C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0571 in 1,240,492 control chromosomes in the GnomAD database, including 3,012 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 0.068 (504 hom., cov: 32)
  • Exomes 𝑓: 0.056 (2508 hom.)
• Consequence: CD22 NM_001771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.33

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD22	NM_001771.4	c.2413-142C>T		intron_variant		ENST00000085219.10	NP_001762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD22	ENST00000085219.10	c.2413-142C>T		intron_variant		1	NM_001771.4	ENSP00000085219.4

Frequencies

GnomAD3 genomes AF: 0.0684 AC: 10394 AN: 152062 Hom.: 501 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.0363

Gnomad ASJ AF: 0.0389

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.0533

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0403

Gnomad OTH AF: 0.0556

GnomAD4 exome AF: 0.0555 AC: 60436 AN: 1088312 Hom.: 2508 AF XY: 0.0578 AC XY: 31536 AN XY: 545560

Gnomad4 AFR exome AF: 0.105

Gnomad4 AMR exome AF: 0.0250

Gnomad4 ASJ exome AF: 0.0404

Gnomad4 EAS exome AF: 0.163

Gnomad4 SAS exome AF: 0.137

Gnomad4 FIN exome AF: 0.0544

Gnomad4 NFE exome AF: 0.0439

Gnomad4 OTH exome AF: 0.0637

GnomAD4 genome AF: 0.0685 AC: 10424 AN: 152180 Hom.: 504 Cov.: 32 AF XY: 0.0707 AC XY: 5260 AN XY: 74412

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.0361

Gnomad4 ASJ AF: 0.0389

Gnomad4 EAS AF: 0.190

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.0533

Gnomad4 NFE AF: 0.0404

Gnomad4 OTH AF: 0.0630

Alfa AF: 0.0271 Hom.: 15

Bravo AF: 0.0672

Asia WGS AF: 0.186 AC: 646 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.057
DANN	Benign	0.69

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

Publications

LitVar

Other links and lift over

dbSNP: rs58156121; hg19: chr19-35837327;