rs851712

Variant names:

• chr7-147831639-A-G
• rs851712
• NM_014141.6:c.2099-71926A>G

Your query was ambiguous. Multiple possible variants found:

• chr7-147831639-A-G
• chr7-147831639-A-T

Variant summary

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

The NM_014141.6(CNTNAP2):​c.2099-71926A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 152,056 control chromosomes in the GnomAD database, including 26,466 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 0.59 (26466 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: CNTNAP2 NM_014141.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.391
• Publications: 4 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]

RNU6-1184P (HGNC:48147): (RNA, U6 small nuclear 1184, pseudogene)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.682 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTNAP2	NM_014141.6	MANE Select	c.2099-71926A>G		intron	N/A	NP_054860.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTNAP2	ENST00000361727.8	TSL:1 MANE Select	c.2099-71926A>G		intron	N/A	ENSP00000354778.3
	CNTNAP2	ENST00000455301.2	TSL:3	n.34-71926A>G		intron	N/A
	CNTNAP2	ENST00000627772.2	TSL:2	n.272-71926A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.586 AC: 88997 AN: 151938 Hom.: 26439 Cov.: 32

Gnomad AFR AF: 0.659

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.593

Gnomad ASJ AF: 0.665

Gnomad EAS AF: 0.701

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.498

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.545

Gnomad OTH AF: 0.627

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

GnomAD4 genome AF: 0.586 AC: 89070 AN: 152056 Hom.: 26466 Cov.: 32 AF XY: 0.583 AC XY: 43346 AN XY: 74342

African (AFR) AF: 0.660 AC: 27346 AN: 41464

American (AMR) AF: 0.593 AC: 9055 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.665 AC: 2309 AN: 3470

East Asian (EAS) AF: 0.701 AC: 3622 AN: 5170

South Asian (SAS) AF: 0.540 AC: 2608 AN: 4830

European-Finnish (FIN) AF: 0.498 AC: 5261 AN: 10568

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.545 AC: 37028 AN: 67962

Other (OTH) AF: 0.630 AC: 1331 AN: 2114

Alfa AF: 0.564 Hom.: 103793

Bravo AF: 0.600

Asia WGS AF: 0.674 AC: 2345 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.42
DANN	Benign	0.50
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: rs851712; hg19: chr7-147528731; COSMIC: COSV62266524; COSMIC: COSV62266524;