chr11-64713505-C-G

Variant names:

• chr11-64713505-C-G
• rs200025059
• NM_015080.4:c.195G>C

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_015080.4(NRXN2):​c.195G>C​(p.Leu65Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000191 in 1,519,486 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000040 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: NRXN2 NM_015080.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.98
• Publications: 1 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 Gene-Disease associations (from GenCC):

• autism

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: G2P, Ambry Genetics
• neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 11-64713505-C-G is Benign according to our data. Variant chr11-64713505-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 436050.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.98 with no splicing effect.

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.195G>C	p.Leu65Leu	synonymous	Exon 2 of 23	NP_055895.1
	NRXN2	NM_138732.3		c.195G>C	p.Leu65Leu	synonymous	Exon 2 of 20	NP_620060.1
	NRXN2	NM_001376262.1		c.195G>C	p.Leu65Leu	synonymous	Exon 2 of 23	NP_001363191.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRXN2	ENST00000265459.11	TSL:5 MANE Select	c.195G>C	p.Leu65Leu	synonymous	Exon 2 of 23	ENSP00000265459.5
	NRXN2	ENST00000704782.1		c.195G>C	p.Leu65Leu	synonymous	Exon 1 of 22	ENSP00000516031.1
	NRXN2	ENST00000377559.7	TSL:1	c.195G>C	p.Leu65Leu	synonymous	Exon 2 of 20	ENSP00000366782.3

Frequencies

GnomAD3 genomes AF: 0.0000396 AC: 6 AN: 151608 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000394

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000167 AC: 23 AN: 138048 AF XY: 0.000155

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000979

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000168 AC: 23 AN: 1367770 Hom.: 0 Cov.: 34 AF XY: 0.0000192 AC XY: 13 AN XY: 677454

African (AFR) AF: 0.00 AC: 0 AN: 28770

American (AMR) AF: 0.000661 AC: 23 AN: 34784

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23936

East Asian (EAS) AF: 0.00 AC: 0 AN: 32528

South Asian (SAS) AF: 0.00 AC: 0 AN: 77420

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34680

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4318

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1074698

Other (OTH) AF: 0.00 AC: 0 AN: 56636

GnomAD4 genome AF: 0.0000395 AC: 6 AN: 151716 Hom.: 0 Cov.: 33 AF XY: 0.0000270 AC XY: 2 AN XY: 74174

African (AFR) AF: 0.00 AC: 0 AN: 41506

American (AMR) AF: 0.000394 AC: 6 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10354

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67848

Other (OTH) AF: 0.00 AC: 0 AN: 2104

Alfa AF: 0.0000942 Hom.: 0

Bravo AF: 0.0000680

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	11
DANN	Benign	0.92
PhyloP100		3.0
PromoterAI		0.0074	Neutral

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: rs200025059; hg19: chr11-64480977;