11-64650833-G-A

Position:

• chr11-64650833-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015080.4(NRXN2):​c.2919-195C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 151,944 control chromosomes in the GnomAD database, including 5,494 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.26 (5494 hom., cov: 31)
• Consequence: NRXN2 NM_015080.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00200

Genes affected

NRXN2 (HGNC:8009): (neurexin 2) This gene encodes a member of the neurexin gene family. The products of these genes function as cell adhesion molecules and receptors in the vertebrate nervous system. These genes utilize two promoters. The majority of transcripts are produced from the upstream promoter and encode alpha-neurexin isoforms while a smaller number of transcripts are produced from the downstream promoter and encode beta-neuresin isoforms. The alpha-neurexins contain epidermal growth factor-like (EGF-like) sequences and laminin G domains, and have been shown to interact with neurexophilins. The beta-neurexins lack EGF-like sequences and contain fewer laminin G domains than alpha-neurexins. Alternative splicing and the use of alternative promoters may generate thousands of transcript variants (PMID: 12036300, PMID: 11944992).[provided by RefSeq, Jun 2010]

NRXN2-AS1 (HGNC:40416): (NRXN2 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 11-64650833-G-A is Benign according to our data. Variant chr11-64650833-G-A is described in ClinVar as [Benign]. Clinvar id is 1230516.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRXN2	NM_015080.4	c.2919-195C>T		intron_variant		ENST00000265459.11	NP_055895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRXN2	ENST00000265459.11	c.2919-195C>T		intron_variant		5	NM_015080.4	ENSP00000265459	P4
NRXN2-AS1	ENST00000433606.1	n.180+4255G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38835 AN: 151826 Hom.: 5482 Cov.: 31

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.256 AC: 38888 AN: 151944 Hom.: 5494 Cov.: 31 AF XY: 0.258 AC XY: 19195 AN XY: 74260

Gnomad4 AFR AF: 0.345

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.478

Gnomad4 SAS AF: 0.210

Gnomad4 FIN AF: 0.298

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.220

Alfa AF: 0.207 Hom.: 3137

Bravo AF: 0.256

Asia WGS AF: 0.333 AC: 1154 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.3
DANN	Benign	0.57

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

Publications

LitVar

Other links and lift over

dbSNP: rs2285339; hg19: chr11-64418305;