19-35337812-A-G

Position:

• chr19-35337812-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001771.4(CD22):​c.776A>G​(p.Asp259Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CD22 NM_001771.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.356

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13657084).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD22	NM_001771.4	c.776A>G	p.Asp259Gly	missense_variant	5/14	ENST00000085219.10	NP_001762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD22	ENST00000085219.10	c.776A>G	p.Asp259Gly	missense_variant	5/14	1	NM_001771.4	ENSP00000085219.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 04, 2024

The c.776A>G (p.D259G) alteration is located in exon 5 (coding exon 4) of the CD22 gene. This alteration results from a A to G substitution at nucleotide position 776, causing the aspartic acid (D) at amino acid position 259 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	11
DANN	Benign	0.97
DEOGEN2	Benign	0.41	.;T;.;.
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.090	N
LIST_S2	Benign	0.57	T;T;T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.14	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L;L;L;.
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-3.0	D;D;D;D
REVEL	Benign	0.033
Sift	Benign	0.13	T;D;D;D
Sift4G	Benign	0.12	T;T;T;T
Polyphen		0.70	.;P;.;.
Vest4		0.19
MutPred		0.52		Gain of catalytic residue at S260 (P = 0.0718);Gain of catalytic residue at S260 (P = 0.0718);Gain of catalytic residue at S260 (P = 0.0718);.;
MVP		0.45
MPC		0.17
ClinPred		0.072	T
GERP RS		1.7
Varity_R		0.33
gMVP		0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-35828715;