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GeneBe

2-124242303-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_ModerateBP6_Very_StrongBP7

The NM_001367498.1(CNTNAP5):c.291C>T(p.Tyr97=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000205 in 1,612,630 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00021 ( 1 hom. )

Consequence

CNTNAP5
NM_001367498.1 synonymous

Scores

2

Clinical Significance

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

Conservation

PhyloP100: -0.685
Variant links:
Genes affected
CNTNAP5 (HGNC:18748): (contactin associated protein family member 5) This gene product belongs to the neurexin family, members of which function in the vertebrate nervous system as cell adhesion molecules and receptors. This protein, like other neurexin proteins, contains epidermal growth factor repeats and laminin G domains. In addition, it includes an F5/8 type C domain, discoidin/neuropilin- and fibrinogen-like domains, and thrombospondin N-terminal-like domains. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
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=-0.44).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 2-124242303-C-T is Benign according to our data. Variant chr2-124242303-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 710619.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=-0.685 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CNTNAP5NM_001367498.1 linkuse as main transcriptc.291C>T p.Tyr97= synonymous_variant 3/24 ENST00000682447.1
CNTNAP5NM_130773.4 linkuse as main transcriptc.291C>T p.Tyr97= synonymous_variant 3/24
CNTNAP5XM_017003316.2 linkuse as main transcriptc.291C>T p.Tyr97= synonymous_variant 3/23

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CNTNAP5ENST00000682447.1 linkuse as main transcriptc.291C>T p.Tyr97= synonymous_variant 3/24 NM_001367498.1 A1
CNTNAP5ENST00000431078.1 linkuse as main transcriptc.291C>T p.Tyr97= synonymous_variant 3/241 P4
CNTNAP5ENST00000470921.1 linkuse as main transcriptn.209C>T non_coding_transcript_exon_variant 2/25

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000158
AC:
24
AN:
152074
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000328
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000206
Gnomad OTH
AF:
0.00144
GnomAD3 exomes
AF:
0.000239
AC:
59
AN:
247016
Hom.:
1
AF XY:
0.000246
AC XY:
33
AN XY:
134000
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000292
Gnomad ASJ exome
AF:
0.000300
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000198
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000339
Gnomad OTH exome
AF:
0.000334
GnomAD4 exome
AF:
0.000210
AC:
307
AN:
1460556
Hom.:
1
Cov.:
31
AF XY:
0.000227
AC XY:
165
AN XY:
726480
show subpopulations
Gnomad4 AFR exome
AF:
0.000239
Gnomad4 AMR exome
AF:
0.000427
Gnomad4 ASJ exome
AF:
0.000192
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000209
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.000179
Gnomad4 OTH exome
AF:
0.000464
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000158
AC:
24
AN:
152074
Hom.:
0
Cov.:
32
AF XY:
0.000148
AC XY:
11
AN XY:
74280
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000328
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000206
Gnomad4 OTH
AF:
0.00144
Alfa
AF:
0.000294
Hom.:
0
Bravo
AF:
0.000212

ClinVar

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

Submissions by phenotype

CNTNAP5-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesMar 29, 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). -
not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeMay 14, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.44
Cadd
Benign
3.0
Dann
Benign
0.67

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.

Other links and lift over

dbSNP: rs369801109; hg19: chr2-124999880; COSMIC: COSV70477419; API