19-35332786-G-A

Position:

• chr19-35332786-G-A

Variant summary

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

The NM_001278417.2(CD22):​c.-130G>A variant causes a 5 prime UTR premature start codon gain 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CD22 NM_001278417.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.89

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=0.2159046).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD22	NM_001771.4	c.274G>A	p.Val92Met	missense_variant	3/14	ENST00000085219.10	NP_001762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD22	ENST00000085219.10	c.274G>A	p.Val92Met	missense_variant	3/14	1	NM_001771.4	ENSP00000085219.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Oct 25, 2024

The c.274G>A (p.V92M) alteration is located in exon 3 (coding exon 2) of the CD22 gene. This alteration results from a G to A substitution at nucleotide position 274, causing the valine (V) at amino acid position 92 to be replaced by a methionine (M). 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	Uncertain	0.40
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T;.;.;.;T;T;.;T;.;T;.;.
Eigen	Benign	0.078
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.42	N
LIST_S2	Uncertain	0.93	D;D;D;D;D;D;D;D;D;D;D;.
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.22	T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.3	.;M;.;.;.;.;.;.;M;M;M;M
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-2.0	.;N;.;.;.;.;.;.;N;N;N;.
REVEL	Benign	0.13
Sift	Uncertain	0.027	.;D;.;.;.;.;.;.;T;D;D;.
Sift4G	Pathogenic	0.0	D;D;D;D;D;D;D;D;D;D;D;D
Polyphen		1.0	.;D;.;.;.;.;.;.;.;D;.;D
Vest4		0.22, 0.23, 0.18, 0.20, 0.28
MutPred		0.40		Gain of disorder (P = 0.0969);Gain of disorder (P = 0.0969);.;Gain of disorder (P = 0.0969);.;Gain of disorder (P = 0.0969);.;Gain of disorder (P = 0.0969);Gain of disorder (P = 0.0969);Gain of disorder (P = 0.0969);Gain of disorder (P = 0.0969);Gain of disorder (P = 0.0969);
MVP		0.51
MPC		0.58
ClinPred		0.58	D
GERP RS		1.7
Varity_R		0.30
gMVP		0.65

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-35823689; COSMIC: COSV105027649; COSMIC: COSV105027649;