Variant 3-140448648-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_022131.3(CLSTN2):c.917T>A(p.Ile306Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00524 in 1,614,080 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0036 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0054 ( 30 hom. )

Consequence

CLSTN2
NM_022131.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 8.02

Variant links:

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]

CLSTN2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.033489287).

BP6

Variant 3-140448648-T-A is Benign according to our data. Variant chr3-140448648-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 771136.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLSTN2	NM_022131.3 linkuse as main transcript	c.917T>A	p.Ile306Asn	missense_variant	6/17	ENST00000458420.7
CLSTN2	XM_017007022.3 linkuse as main transcript	c.842T>A	p.Ile281Asn	missense_variant	6/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLSTN2	ENST00000458420.7 linkuse as main transcript	c.917T>A	p.Ile306Asn	missense_variant	6/17	1	NM_022131.3	P1
CLSTN2	ENST00000511524.1 linkuse as main transcript	n.1105T>A		non_coding_transcript_exon_variant	6/11	2

Frequencies

GnomAD3 genomes

AF:

0.00358

AC:

545

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00138

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.0109

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00567

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00356

AC:

894

AN:

251248

Hom.:

AF XY:

0.00366

AC XY:

497

AN XY:

135768

show subpopulations

Gnomad AFR exome

AF:

0.00141

Gnomad AMR exome

AF:

0.00136

Gnomad ASJ exome

AF:

0.00754

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00206

Gnomad FIN exome

AF:

0.00176

Gnomad NFE exome

AF:

0.00554

Gnomad OTH exome

AF:

0.00294

GnomAD4 exome

AF:

0.00541

AC:

7907

AN:

1461794

Hom.:

Cov.:

AF XY:

0.00531

AC XY:

3865

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.000986

Gnomad4 AMR exome

AF:

0.00143

Gnomad4 ASJ exome

AF:

0.00811

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00225

Gnomad4 FIN exome

AF:

0.00163

Gnomad4 NFE exome

AF:

0.00635

Gnomad4 OTH exome

AF:

0.00387

GnomAD4 genome

AF:

0.00359

AC:

547

AN:

152286

Hom.:

Cov.:

AF XY:

0.00332

AC XY:

247

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00137

Gnomad4 AMR

AF:

0.00242

Gnomad4 ASJ

AF:

0.0109

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.000942

Gnomad4 NFE

AF:

0.00567

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.00448

Hom.:

Bravo

AF:

0.00341

TwinsUK

AF:

0.00674

AC:

ALSPAC

AF:

0.00545

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.00605

AC:

ExAC

AF:

0.00327

AC:

397

EpiCase

AF:

0.00622

EpiControl

AF:

0.00563

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2022	CLSTN2: BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.73

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Uncertain

-0.020

Cadd

Pathogenic

Dann

Uncertain

0.99

DEOGEN2

Uncertain

0.70

Eigen

Pathogenic

0.80

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.98

M_CAP

Uncertain

0.098

MetaRNN

Benign

0.033

MetaSVM

Benign

-0.36

MutationAssessor

Uncertain

2.7

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.71

PROVEAN

Pathogenic

-5.7

REVEL

Uncertain

0.49

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.91

MVP

0.90

MPC

0.97

ClinPred

0.030

GERP RS

5.2

Varity_R

0.86

gMVP

0.78

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over