7-147343905-A-G

Variant names:

• chr7-147343905-A-G
• rs7803992
• NM_014141.6:c.1498+43615A>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.1498+43615A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.642 in 152,000 control chromosomes in the GnomAD database, including 32,411 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 0.64 (32411 hom., cov: 32)
• Consequence: CNTNAP2 NM_014141.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.806
• Publications: 3 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.817 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTNAP2	NM_014141.6	c.1498+43615A>G		intron_variant	Intron 9 of 23	ENST00000361727.8	NP_054860.1
CNTNAP2	XM_017011950.3	c.1498+43615A>G		intron_variant	Intron 9 of 13		XP_016867439.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTNAP2	ENST00000361727.8	c.1498+43615A>G		intron_variant	Intron 9 of 23	1	NM_014141.6	ENSP00000354778.3

Frequencies

GnomAD3 genomes AF: 0.642 AC: 97433 AN: 151882 Hom.: 32361 Cov.: 32

Gnomad AFR AF: 0.824

Gnomad AMI AF: 0.592

Gnomad AMR AF: 0.589

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.562

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.584

Gnomad OTH AF: 0.571

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

GnomAD4 genome AF: 0.642 AC: 97533 AN: 152000 Hom.: 32411 Cov.: 32 AF XY: 0.637 AC XY: 47341 AN XY: 74278

African (AFR) AF: 0.824 AC: 34186 AN: 41478

American (AMR) AF: 0.589 AC: 8994 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.549 AC: 1904 AN: 3466

East Asian (EAS) AF: 0.418 AC: 2159 AN: 5162

South Asian (SAS) AF: 0.562 AC: 2706 AN: 4816

European-Finnish (FIN) AF: 0.568 AC: 5995 AN: 10560

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.584 AC: 39707 AN: 67938

Other (OTH) AF: 0.567 AC: 1196 AN: 2110

Alfa AF: 0.615 Hom.: 5235

Bravo AF: 0.650

Asia WGS AF: 0.481 AC: 1674 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.1
DANN	Benign	0.57
PhyloP100		-0.81
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: rs7803992; hg19: chr7-147040997;