chr11-64713030-G-C

Variant names:

• chr11-64713030-G-C
• NM_015080.4:c.670C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015080.4(NRXN2):​c.670C>G​(p.Pro224Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000766 in 1,305,346 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.7e-7 (0 hom.)
• Consequence: NRXN2 NM_015080.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.86

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.222704).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRXN2	NM_015080.4	c.670C>G	p.Pro224Ala	missense_variant	Exon 2 of 23	ENST00000265459.11	NP_055895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRXN2	ENST00000265459.11	c.670C>G	p.Pro224Ala	missense_variant	Exon 2 of 23	5	NM_015080.4	ENSP00000265459.5
NRXN2	ENST00000704782.1	c.670C>G	p.Pro224Ala	missense_variant	Exon 1 of 22			ENSP00000516031.1
NRXN2	ENST00000704781.1	c.670C>G	p.Pro224Ala	missense_variant	Exon 1 of 22			ENSP00000516029.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.66e-7 AC: 1 AN: 1305346 Hom.: 0 Cov.: 29 AF XY: 0.00000156 AC XY: 1 AN XY: 640566

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000366

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.039	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.0087	T;.;T;.
Eigen	Benign	-0.092
Eigen_PC	Benign	-0.037
FATHMM_MKL	Benign	0.59	D
LIST_S2	Uncertain	0.89	.;D;D;D
M_CAP	Pathogenic	0.56	D
MetaRNN	Benign	0.22	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.20	N;N;N;.
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.92	N;N;N;N
REVEL	Benign	0.10
Sift	Uncertain	0.026	D;D;D;D
Sift4G	Uncertain	0.011	D;D;D;D
Polyphen		0.038	B;B;B;.
Vest4		0.19
MutPred		0.56		Loss of disorder (P = 0.0682);Loss of disorder (P = 0.0682);Loss of disorder (P = 0.0682);Loss of disorder (P = 0.0682);
MVP		0.10
MPC		0.59
ClinPred		0.27	T
GERP RS		3.3
Varity_R		0.096
gMVP		0.25

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-64480502;