rs786204800

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5

The ENST00000591662.1(CNTNAP1):n.*754-2_*755delAGAT variant causes a splice region, non coding transcript exon change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,447,102 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CNTNAP1
ENST00000591662.1 splice_region, non_coding_transcript_exon

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 8.07

Publications

1 publications found

Variant links:

Genes affected

CNTNAP1 (HGNC:8011): (contactin associated protein 1) The gene product was initially identified as a 190-kD protein associated with the contactin-PTPRZ1 complex. The 1,384-amino acid protein, also designated p190 or CASPR for 'contactin-associated protein,' includes an extracellular domain with several putative protein-protein interaction domains, a putative transmembrane domain, and a 74-amino acid cytoplasmic domain. Northern blot analysis showed that the gene is transcribed predominantly in brain as a transcript of 6.2 kb, with weak expression in several other tissues tested. The architecture of its extracellular domain is similar to that of neurexins, and this protein may be the signaling subunit of contactin, enabling recruitment and activation of intracellular signaling pathways in neurons. [provided by RefSeq, Jan 2009]

CNTNAP1 Gene-Disease associations (from GenCC):

lethal congenital contracture syndrome 7
Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
hypomyelination neuropathy-arthrogryposis syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CNTNAP1 links:

ENSG00000267765 (HGNC:58591):

ENSG00000267765 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

PP5

Variant 17-42695518-CAGAT-C is Pathogenic according to our data. Variant chr17-42695518-CAGAT-C is described in ClinVar as Pathogenic. ClinVar VariationId is 189262.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTNAP1	NM_003632.3 link	c.2993-1_2995delGATA	p.Asp998_Ile999delinsVal	splice_acceptor_variant, disruptive_inframe_deletion, splice_region_variant, intron_variant	Exon 19 of 24	ENST00000264638.9	NP_003623.1	P78357

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CNTNAP1	ENST00000591662.1 link	n.754-2_755delAGAT		splice_region_variant, non_coding_transcript_exon_variant	Exon 19 of 24	1		ENSP00000466571.1	K7EMM9
CNTNAP1	ENST00000264638.9 link	c.2993-2_2994delAGAT	p.Ile999fs	frameshift_variant, splice_acceptor_variant, splice_region_variant, intron_variant	Exon 19 of 24	1	NM_003632.3	ENSP00000264638.3	P78357
CNTNAP1	ENST00000591662.1 link	n.754-2_755delAGAT		splice_acceptor_variant, 3_prime_UTR_variant, intron_variant	Exon 19 of 24	1		ENSP00000466571.1	K7EMM9
ENSG00000267765	ENST00000592440.1 link	n.363+3582_363+3585delATCT		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000410

AC:

AN:

243996

AF XY:

0.00000753

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000910

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.91e-7

AC:

AN:

1447102

Hom.:

AF XY:

0.00000139

AC XY:

AN XY:

717168

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33146

American (AMR)

AF:

0.00

AC:

AN:

44070

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25714

East Asian (EAS)

AF:

0.00

AC:

AN:

39308

South Asian (SAS)

AF:

0.00

AC:

AN:

85558

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52972

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5722

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1100926

Other (OTH)

AF:

0.0000168

AC:

AN:

59686

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Lethal congenital contracture syndrome 7

Pathogenic:1

May 01, 2014

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

8.1

Mutation Taster

=0/200

disease causing (ClinVar)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

1.0

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.45

Position offset: 23

DS_AL_spliceai

1.0

Position offset: 3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over