rs2350488

chr3-140066032-A-Gchr3-140066032-A-T

Variant summary

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

The NM_022131.3(CLSTN2):c.110-109919A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 152,032 control chromosomes in the GnomAD database, including 25,542 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 0.56 (25542 hom., cov: 33)
• Consequence: CLSTN2 NM_022131.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.263

Genes affected

CLSTN2 (HGNC:17448): (calsyntenin 2) Predicted to enable calcium ion binding activity. Predicted to be involved in positive regulation of synapse assembly and positive regulation of synaptic transmission. Predicted to be located in postsynaptic density. Predicted to be active in cell surface; glutamatergic synapse; and postsynaptic membrane. Predicted to be integral component of postsynaptic density membrane. [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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.746 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLSTN2	NM_022131.3	c.110-109919A>G		intron_variant		ENST00000458420.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLSTN2	ENST00000458420.7	c.110-109919A>G		intron_variant		1	NM_022131.3	P1
CLSTN2	ENST00000511524.1	n.298-109919A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85622 AN: 151914 Hom.: 25492 Cov.: 33

Gnomad AFR AF: 0.753

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.633

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.619

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.478

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.466

Gnomad OTH AF: 0.538

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.564 AC: 85734 AN: 152032 Hom.: 25542 Cov.: 33 AF XY: 0.565 AC XY: 41973 AN XY: 74316

Gnomad4 AFR AF: 0.753

Gnomad4 AMR AF: 0.633

Gnomad4 ASJ AF: 0.313

Gnomad4 EAS AF: 0.620

Gnomad4 SAS AF: 0.446

Gnomad4 FIN AF: 0.478

Gnomad4 NFE AF: 0.466

Gnomad4 OTH AF: 0.537

Alfa AF: 0.492 Hom.: 18603

Bravo AF: 0.586

Asia WGS AF: 0.503 AC: 1752 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.2
Dann	Benign	0.35

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: rs2350488; hg19: chr3-139784874;