11-64648431-C-T

Variant names:

• chr11-64648431-C-T
• rs59739006
• NM_015080.4:c.3284-93G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015080.4(NRXN2):​c.3284-93G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 1,588,384 control chromosomes in the GnomAD database, including 17,343 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1354 hom., cov: 32)
  • Exomes 𝑓: 0.15 (15989 hom.)
• Consequence: NRXN2 NM_015080.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.316
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 11-64648431-C-T is Benign according to our data. Variant chr11-64648431-C-T is described in ClinVar as Benign. ClinVar VariationId is 1253337.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015080.4. 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
	NRXN2	NM_015080.4	MANE Select	c.3284-93G>A		intron	N/A	NP_055895.1	Q9P2S2-1
	NRXN2	NM_138732.3		c.3164-93G>A		intron	N/A	NP_620060.1	Q9P2S2-2
	NRXN2	NM_001376262.1		c.3284-93G>A		intron	N/A	NP_001363191.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRXN2	ENST00000265459.11	TSL:5 MANE Select	c.3284-93G>A		intron	N/A	ENSP00000265459.5	Q9P2S2-1
	NRXN2	ENST00000704782.1		c.3293-93G>A		intron	N/A	ENSP00000516031.1	A0A994J5C3
	NRXN2	ENST00000377559.7	TSL:1	c.3164-93G>A		intron	N/A	ENSP00000366782.3	Q9P2S2-2

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17519 AN: 152130 Hom.: 1355 Cov.: 32

Gnomad AFR AF: 0.0299

Gnomad AMI AF: 0.0824

Gnomad AMR AF: 0.0888

Gnomad ASJ AF: 0.0495

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.110

GnomAD4 exome AF: 0.145 AC: 208298 AN: 1436136 Hom.: 15989 AF XY: 0.144 AC XY: 103357 AN XY: 715404

African (AFR) AF: 0.0231 AC: 761 AN: 32930

American (AMR) AF: 0.0864 AC: 3810 AN: 44106

Ashkenazi Jewish (ASJ) AF: 0.0530 AC: 1373 AN: 25896

East Asian (EAS) AF: 0.209 AC: 8267 AN: 39524

South Asian (SAS) AF: 0.124 AC: 10580 AN: 85364

European-Finnish (FIN) AF: 0.219 AC: 11344 AN: 51750

Middle Eastern (MID) AF: 0.0824 AC: 373 AN: 4524

European-Non Finnish (NFE) AF: 0.150 AC: 163672 AN: 1092632

Other (OTH) AF: 0.137 AC: 8118 AN: 59410

GnomAD4 genome AF: 0.115 AC: 17512 AN: 152248 Hom.: 1354 Cov.: 32 AF XY: 0.119 AC XY: 8857 AN XY: 74434

African (AFR) AF: 0.0299 AC: 1241 AN: 41572

American (AMR) AF: 0.0886 AC: 1355 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0495 AC: 172 AN: 3472

East Asian (EAS) AF: 0.185 AC: 959 AN: 5170

South Asian (SAS) AF: 0.134 AC: 645 AN: 4828

European-Finnish (FIN) AF: 0.243 AC: 2574 AN: 10594

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.151 AC: 10250 AN: 67994

Other (OTH) AF: 0.108 AC: 228 AN: 2112

Alfa AF: 0.128 Hom.: 181

Bravo AF: 0.101

Asia WGS AF: 0.174 AC: 606 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	10
DANN	Benign	0.62
PhyloP100		0.32
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: rs59739006; hg19: chr11-64415903; COSMIC: COSV107207570; COSMIC: COSV107207570;