19-35336078-A-G

Position:

• chr19-35336078-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001771.4(CD22):​c.455A>G​(p.Gln152Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,694 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q152E) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: CD22 NM_001771.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.53

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04957843).
• BP6: Variant 19-35336078-A-G is Benign according to our data. Variant chr19-35336078-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2294447.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD22	NM_001771.4	c.455A>G	p.Gln152Arg	missense_variant	4/14	ENST00000085219.10	NP_001762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD22	ENST00000085219.10	c.455A>G	p.Gln152Arg	missense_variant	4/14	1	NM_001771.4	ENSP00000085219.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461694 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727154

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 09, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.0010
DANN	Benign	0.21
DEOGEN2	Benign	0.23	.;T;.;T;.;.;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.51	T;T;T;T;T;.;T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.050	T;T;T;T;T;T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	0.61	N;.;N;N;N;N;.
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.95	N;.;N;N;N;.;.
REVEL	Benign	0.13
Sift	Benign	0.65	T;.;T;T;T;.;.
Sift4G	Benign	0.92	T;T;T;T;T;T;D
Polyphen		0.070	B;.;.;B;.;B;.
Vest4		0.085
MutPred		0.33		Gain of phosphorylation at S154 (P = 0.135);Gain of phosphorylation at S154 (P = 0.135);Gain of phosphorylation at S154 (P = 0.135);Gain of phosphorylation at S154 (P = 0.135);Gain of phosphorylation at S154 (P = 0.135);Gain of phosphorylation at S154 (P = 0.135);.;
MVP		0.41
MPC		0.14
ClinPred		0.10	T
GERP RS		-5.3
Varity_R		0.22
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1423109494; hg19: chr19-35826981;