rs2710117

Variant names:

• chr7-147904680-T-A
• rs2710117
• NM_014141.6:c.2255+959T>A

Your query was ambiguous. Multiple possible variants found:

• chr7-147904680-T-A
• chr7-147904680-T-C
• chr7-147904680-T-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.2255+959T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.633 in 152,006 control chromosomes in the GnomAD database, including 30,644 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 0.63 (30644 hom., cov: 32)
• Consequence: CNTNAP2 NM_014141.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.394
• Publications: 19 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 (AMR) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014141.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTNAP2	NM_014141.6	MANE Select	c.2255+959T>A		intron	N/A	NP_054860.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTNAP2	ENST00000361727.8	TSL:1 MANE Select	c.2255+959T>A		intron	N/A	ENSP00000354778.3
	CNTNAP2	ENST00000455301.2	TSL:3	n.190+959T>A		intron	N/A
	CNTNAP2	ENST00000627772.2	TSL:2	n.428+959T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.633 AC: 96193 AN: 151888 Hom.: 30622 Cov.: 32

Gnomad AFR AF: 0.620

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.803

Gnomad EAS AF: 0.626

Gnomad SAS AF: 0.609

Gnomad FIN AF: 0.546

Gnomad MID AF: 0.758

Gnomad NFE AF: 0.644

Gnomad OTH AF: 0.676

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

GnomAD4 genome AF: 0.633 AC: 96261 AN: 152006 Hom.: 30644 Cov.: 32 AF XY: 0.629 AC XY: 46692 AN XY: 74278

African (AFR) AF: 0.620 AC: 25683 AN: 41434

American (AMR) AF: 0.654 AC: 10003 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.803 AC: 2784 AN: 3468

East Asian (EAS) AF: 0.626 AC: 3224 AN: 5154

South Asian (SAS) AF: 0.609 AC: 2932 AN: 4818

European-Finnish (FIN) AF: 0.546 AC: 5751 AN: 10542

Middle Eastern (MID) AF: 0.753 AC: 220 AN: 292

European-Non Finnish (NFE) AF: 0.644 AC: 43767 AN: 67992

Other (OTH) AF: 0.678 AC: 1430 AN: 2110

Alfa AF: 0.631 Hom.: 3793

Bravo AF: 0.642

Asia WGS AF: 0.628 AC: 2185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.89
DANN	Benign	0.52
PhyloP100		-0.39
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: rs2710117; hg19: chr7-147601772;