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GeneBe

1-205057955-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS1

The NM_005076.5(CNTN2):c.105C>T(p.Phe35=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00212 in 1,614,148 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0017 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0022 ( 3 hom. )

Consequence

CNTN2
NM_005076.5 synonymous

Scores

2

Clinical Significance

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

Conservation

PhyloP100: -0.264
Variant links:
Genes affected
CNTN2 (HGNC:2172): (contactin 2) This gene encodes a member of the contactin family of proteins, part of the immunoglobulin superfamily of cell adhesion molecules. The encoded glycosylphosphatidylinositol (GPI)-anchored neuronal membrane protein plays a role in the proliferation, migration, and axon guidance of neurons of the developing cerebellum. A mutation in this gene may be associated with adult myoclonic epilepsy. [provided by RefSeq, Sep 2016]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.37).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-205057955-C-T is Benign according to our data. Variant chr1-205057955-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 474457.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.264 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00173 (264/152346) while in subpopulation NFE AF= 0.00293 (199/68034). AF 95% confidence interval is 0.00259. There are 0 homozygotes in gnomad4. There are 128 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CNTN2NM_005076.5 linkuse as main transcriptc.105C>T p.Phe35= synonymous_variant 3/23 ENST00000331830.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CNTN2ENST00000331830.7 linkuse as main transcriptc.105C>T p.Phe35= synonymous_variant 3/231 NM_005076.5 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00173
AC:
264
AN:
152228
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000265
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000654
Gnomad ASJ
AF:
0.00605
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00188
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00292
Gnomad OTH
AF:
0.00143
GnomAD3 exomes
AF:
0.00185
AC:
464
AN:
251128
Hom.:
1
AF XY:
0.00180
AC XY:
244
AN XY:
135726
show subpopulations
Gnomad AFR exome
AF:
0.000369
Gnomad AMR exome
AF:
0.000376
Gnomad ASJ exome
AF:
0.00626
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00250
Gnomad NFE exome
AF:
0.00275
Gnomad OTH exome
AF:
0.00229
GnomAD4 exome
AF:
0.00217
AC:
3165
AN:
1461802
Hom.:
3
Cov.:
32
AF XY:
0.00219
AC XY:
1593
AN XY:
727210
show subpopulations
Gnomad4 AFR exome
AF:
0.000358
Gnomad4 AMR exome
AF:
0.000514
Gnomad4 ASJ exome
AF:
0.00677
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000464
Gnomad4 FIN exome
AF:
0.00266
Gnomad4 NFE exome
AF:
0.00243
Gnomad4 OTH exome
AF:
0.00174
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00173
AC:
264
AN:
152346
Hom.:
0
Cov.:
32
AF XY:
0.00172
AC XY:
128
AN XY:
74502
show subpopulations
Gnomad4 AFR
AF:
0.000264
Gnomad4 AMR
AF:
0.000653
Gnomad4 ASJ
AF:
0.00605
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00188
Gnomad4 NFE
AF:
0.00293
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.00295
Hom.:
1
Bravo
AF:
0.00154
EpiCase
AF:
0.00311
EpiControl
AF:
0.00255

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

CNTN2-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesApr 22, 2019This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Epilepsy, familial adult myoclonic, 5 Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 25, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.37
Cadd
Benign
8.2
Dann
Benign
0.66

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

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

Other links and lift over

dbSNP: rs147074435; hg19: chr1-205027083; API