rs12155129

Variant names:

• chr7-148159773-A-G
• rs12155129
• NM_014141.6:c.2773+12064A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014141.6(CNTNAP2):​c.2773+12064A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0664 in 152,252 control chromosomes in the GnomAD database, including 427 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.066 (427 hom., cov: 32)
• Consequence: CNTNAP2 NM_014141.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.250
• Publications: 2 publications found

Genes affected

CNTNAP2 (HGNC:13830): (contactin associated protein 2) This gene encodes a member of the neurexin family which functions 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, thrombospondin N-terminal-like domains and a putative PDZ binding site. This protein is localized at the juxtaparanodes of myelinated axons, and mediates interactions between neurons and glia during nervous system development and is also involved in localization of potassium channels within differentiating axons. This gene encompasses almost 1.5% of chromosome 7 and is one of the largest genes in the human genome. It is directly bound and regulated by forkhead box protein P2, a transcription factor related to speech and language development. This gene has been implicated in multiple neurodevelopmental disorders, including Gilles de la Tourette syndrome, schizophrenia, epilepsy, autism, ADHD and intellectual disability. [provided by RefSeq, Jul 2017]

CNTNAP2 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR, AD Classification: DEFINITIVE, NO_KNOWN Submitted by: ClinGen
• cortical dysplasia-focal epilepsy syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Illumina, Labcorp Genetics (formerly Invitae), Orphanet, G2P, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTNAP2	NM_014141.6	c.2773+12064A>G		intron_variant	Intron 17 of 23	ENST00000361727.8	NP_054860.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTNAP2	ENST00000361727.8	c.2773+12064A>G		intron_variant	Intron 17 of 23	1	NM_014141.6	ENSP00000354778.3

Frequencies

GnomAD3 genomes AF: 0.0664 AC: 10109 AN: 152134 Hom.: 427 Cov.: 32

Gnomad AFR AF: 0.0244

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.0580

Gnomad ASJ AF: 0.0974

Gnomad EAS AF: 0.00366

Gnomad SAS AF: 0.0899

Gnomad FIN AF: 0.0408

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0994

Gnomad OTH AF: 0.0755

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0664 AC: 10108 AN: 152252 Hom.: 427 Cov.: 32 AF XY: 0.0637 AC XY: 4739 AN XY: 74440

African (AFR) AF: 0.0244 AC: 1012 AN: 41548

American (AMR) AF: 0.0579 AC: 886 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0974 AC: 338 AN: 3470

East Asian (EAS) AF: 0.00366 AC: 19 AN: 5186

South Asian (SAS) AF: 0.0902 AC: 434 AN: 4814

European-Finnish (FIN) AF: 0.0408 AC: 433 AN: 10606

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0994 AC: 6759 AN: 68016

Other (OTH) AF: 0.0747 AC: 158 AN: 2114

Alfa AF: 0.0714 Hom.: 349

Bravo AF: 0.0636

Asia WGS AF: 0.0480 AC: 169 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.8
DANN	Benign	0.62
PhyloP100		-0.25
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12155129; hg19: chr7-147856865;