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GeneBe

1-205073109-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_005076.5(CNTN2):c.2886C>T(p.His962=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00201 in 1,614,186 control chromosomes in the GnomAD database, including 69 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.011 ( 38 hom., cov: 32)
Exomes 𝑓: 0.0011 ( 31 hom. )

Consequence

CNTN2
NM_005076.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.05
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=-0.55).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-205073109-C-T is Benign according to our data. Variant chr1-205073109-C-T is described in ClinVar as [Benign]. Clinvar id is 474480.Status of the report is criteria_provided_single_submitter, 1 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=1.05 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0109 (1667/152320) while in subpopulation AFR AF= 0.0385 (1599/41552). AF 95% confidence interval is 0.0369. There are 38 homozygotes in gnomad4. There are 780 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 39 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CNTN2NM_005076.5 linkuse as main transcriptc.2886C>T p.His962= synonymous_variant 22/23 ENST00000331830.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CNTN2ENST00000331830.7 linkuse as main transcriptc.2886C>T p.His962= synonymous_variant 22/231 NM_005076.5 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0109
AC:
1659
AN:
152202
Hom.:
39
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0384
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00262
Gnomad ASJ
AF:
0.000576
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.00909
GnomAD3 exomes
AF:
0.00290
AC:
729
AN:
251360
Hom.:
13
AF XY:
0.00210
AC XY:
286
AN XY:
135874
show subpopulations
Gnomad AFR exome
AF:
0.0418
Gnomad AMR exome
AF:
0.000810
Gnomad ASJ exome
AF:
0.000595
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000114
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.00108
AC:
1585
AN:
1461866
Hom.:
31
Cov.:
31
AF XY:
0.000943
AC XY:
686
AN XY:
727236
show subpopulations
Gnomad4 AFR exome
AF:
0.0401
Gnomad4 AMR exome
AF:
0.000894
Gnomad4 ASJ exome
AF:
0.000497
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000315
Gnomad4 OTH exome
AF:
0.00237
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0109
AC:
1667
AN:
152320
Hom.:
38
Cov.:
32
AF XY:
0.0105
AC XY:
780
AN XY:
74490
show subpopulations
Gnomad4 AFR
AF:
0.0385
Gnomad4 AMR
AF:
0.00261
Gnomad4 ASJ
AF:
0.000576
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.00900
Alfa
AF:
0.000604
Hom.:
0
Bravo
AF:
0.0126
Asia WGS
AF:
0.00231
AC:
8
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.000296

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Epilepsy, familial adult myoclonic, 5 Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeFeb 01, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.55
Cadd
Benign
5.6
Dann
Benign
0.62

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs56111335; hg19: chr1-205042237; API