rs201107921
Positions:
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 3P and 8B. PM2PP2BP4_ModerateBP6_ModerateBS1
The NM_005076.5(CNTN2):c.2608G>A(p.Asp870Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000874 in 1,614,052 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000090 ( 0 hom. )
Consequence
CNTN2
NM_005076.5 missense
NM_005076.5 missense
Scores
1
3
10
Clinical Significance
Conservation
PhyloP100: 5.46
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 Likely_benign. Variant got -5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, CNTN2
BP4
?
Computational evidence support a benign effect (MetaRNN=0.17766076).
BP6
?
Variant 1-205072010-G-A is Benign according to our data. Variant chr1-205072010-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 541409.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0000896 (131/1461816) while in subpopulation NFE AF= 0.00011 (122/1111990). AF 95% confidence interval is 0.0000938. There are 0 homozygotes in gnomad4_exome. There are 70 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CNTN2 | NM_005076.5 | c.2608G>A | p.Asp870Asn | missense_variant | 20/23 | ENST00000331830.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CNTN2 | ENST00000331830.7 | c.2608G>A | p.Asp870Asn | missense_variant | 20/23 | 1 | NM_005076.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000657 AC: 10AN: 152236Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000836 AC: 21AN: 251268Hom.: 0 AF XY: 0.0000884 AC XY: 12AN XY: 135790
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GnomAD4 exome AF: 0.0000896 AC: 131AN: 1461816Hom.: 0 Cov.: 31 AF XY: 0.0000963 AC XY: 70AN XY: 727206
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GnomAD4 genome ? AF: 0.0000657 AC: 10AN: 152236Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74370
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Epilepsy, familial adult myoclonic, 5 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 18, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;.
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;.
MutationTaster
Benign
D
PrimateAI
Uncertain
T
Polyphen
B;B;.
Vest4
0.24
MVP
0.77
MPC
0.60
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at