rs561309225

Variant names:

• chr17-7408583-C-A
• rs561309225
• NM_020795.4:c.328C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-7408583-C-A
• chr17-7408583-C-G
• chr17-7408583-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020795.4(NLGN2):​c.328C>A​(p.Leu110Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000706 in 1,415,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L110L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: NLGN2 NM_020795.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.210
• Publications: 0 publications found

Genes affected

NLGN2 (HGNC:14290): (neuroligin 2) This gene encodes a member of a family of neuronal cell surface proteins. Members of this family may act as splice site-specific ligands for beta-neurexins and may be involved in the formation and remodeling of central nervous system synapses. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21989506).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020795.4. 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
	NLGN2	NM_020795.4	MANE Select	c.328C>A	p.Leu110Met	missense	Exon 1 of 7	NP_065846.1	Q8NFZ4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLGN2	ENST00000302926.7	TSL:1 MANE Select	c.328C>A	p.Leu110Met	missense	Exon 1 of 7	ENSP00000305288.2	Q8NFZ4
	NLGN2	ENST00000575301.5	TSL:5	c.328C>A	p.Leu110Met	missense	Exon 2 of 8	ENSP00000461168.1	Q8NFZ4
	NLGN2	ENST00000570940.1	TSL:3	c.-60C>A		upstream_gene	N/A	ENSP00000461092.1	I3L498

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.06e-7 AC: 1 AN: 1415798 Hom.: 0 Cov.: 34 AF XY: 0.00000143 AC XY: 1 AN XY: 700766

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32160

American (AMR) AF: 0.0000264 AC: 1 AN: 37822

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25296

East Asian (EAS) AF: 0.00 AC: 0 AN: 36680

South Asian (SAS) AF: 0.00 AC: 0 AN: 81176

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47512

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5650

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1090770

Other (OTH) AF: 0.00 AC: 0 AN: 58732

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
Eigen	Benign	0.15
Eigen_PC	Benign	0.15
FATHMM_MKL	Benign	0.52	D
M_CAP	Uncertain	0.094	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.48	T
MutationAssessor	Benign	0.87	L
PhyloP100		0.21
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.64	N
REVEL	Benign	0.11
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.11	T
Polyphen		0.66	P
Vest4		0.22
MutPred		0.38		Gain of disorder (P = 0.1336)
MVP		0.24
MPC		1.6
ClinPred		0.70	D
GERP RS		3.4
PromoterAI		-0.028	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.36
gMVP		0.65

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: rs561309225; hg19: chr17-7311902;