rs10406069

Positions:

• chr19-35345627-G-A
• chr19-35345627-G-C

Variant summary

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

The NM_001771.4(CD22):​c.2234G>A​(p.Gly745Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 1,609,258 control chromosomes in the GnomAD database, including 29,083 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.15 (2179 hom., cov: 30)
  • Exomes 𝑓: 0.19 (26904 hom.)
• Consequence: CD22 NM_001771.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.111

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]

MIR5196 (HGNC:43542): (microRNA 5196) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0034743845).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD22	NM_001771.4	c.2234G>A	p.Gly745Asp	missense_variant	12/14	ENST00000085219.10
MIR5196	NR_049828.1	n.115G>A		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD22	ENST00000085219.10	c.2234G>A	p.Gly745Asp	missense_variant	12/14	1	NM_001771.4	P2
MIR5196	ENST00000578146.1	n.115G>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23478 AN: 151720 Hom.: 2180 Cov.: 30

Gnomad AFR AF: 0.0681

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.0856

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.158

GnomAD3 exomes AF: 0.165 AC: 41386 AN: 251022 Hom.: 3900 AF XY: 0.166 AC XY: 22501 AN XY: 135702

Gnomad AFR exome AF: 0.0653

Gnomad AMR exome AF: 0.0910

Gnomad ASJ exome AF: 0.172

Gnomad EAS exome AF: 0.236

Gnomad SAS exome AF: 0.0760

Gnomad FIN exome AF: 0.182

Gnomad NFE exome AF: 0.210

Gnomad OTH exome AF: 0.173

GnomAD4 exome AF: 0.186 AC: 271741 AN: 1457422 Hom.: 26904 Cov.: 31 AF XY: 0.184 AC XY: 133250 AN XY: 725332

Gnomad4 AFR exome AF: 0.0602

Gnomad4 AMR exome AF: 0.0962

Gnomad4 ASJ exome AF: 0.166

Gnomad4 EAS exome AF: 0.202

Gnomad4 SAS exome AF: 0.0800

Gnomad4 FIN exome AF: 0.182

Gnomad4 NFE exome AF: 0.203

Gnomad4 OTH exome AF: 0.181

GnomAD4 genome AF: 0.155 AC: 23467 AN: 151836 Hom.: 2179 Cov.: 30 AF XY: 0.153 AC XY: 11382 AN XY: 74184

Gnomad4 AFR AF: 0.0679

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.169

Gnomad4 EAS AF: 0.231

Gnomad4 SAS AF: 0.0853

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.202

Gnomad4 OTH AF: 0.159

Alfa AF: 0.189 Hom.: 6640

Bravo AF: 0.149

TwinsUK AF: 0.198 AC: 733

ALSPAC AF: 0.195 AC: 751

ESP6500AA AF: 0.0713 AC: 314

ESP6500EA AF: 0.207 AC: 1781

ExAC AF: 0.170 AC: 20589

Asia WGS AF: 0.149 AC: 519 AN: 3478

EpiCase AF: 0.201

EpiControl AF: 0.202

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	10
DANN	Benign	0.70
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.57	T;T;T;T;.
MetaRNN	Benign	0.0035	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	P;P;P;P;P;P
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-3.0	D;D;D;D;.
REVEL	Benign	0.013
Sift	Benign	0.17	T;T;T;T;.
Sift4G	Benign	0.29	T;T;T;T;T
Polyphen		0.082	B;.;B;.;B
Vest4		0.14
MPC		0.20
ClinPred		0.011	T
GERP RS		-1.4
Varity_R		0.16
gMVP		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs10406069; hg19: chr19-35836530; COSMIC: COSV50050834; COSMIC: COSV50050834;