17-7408532-T-TGGCCCGGCGTGC

Variant names:

• chr17-7408532-T-TGGCCCGGCGTGC
• NM_020795.4:c.279_290dupGCCCGGCGTGCG

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP3 BP3

The NM_020795.4(NLGN2):​c.279_290dupGCCCGGCGTGCG​(p.Arg97_Asn98insProGlyValArg) variant causes a disruptive inframe insertion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: NLGN2 NM_020795.4 disruptive_inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.12

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
• BP3: Nonframeshift variant in repetitive region in NM_020795.4

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLGN2	NM_020795.4	c.279_290dupGCCCGGCGTGCG	p.Arg97_Asn98insProGlyValArg	disruptive_inframe_insertion	Exon 1 of 7	ENST00000302926.7	NP_065846.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NLGN2	ENST00000302926.7	c.279_290dupGCCCGGCGTGCG	p.Arg97_Asn98insProGlyValArg	disruptive_inframe_insertion	Exon 1 of 7	1	NM_020795.4	ENSP00000305288.2
NLGN2	ENST00000575301.5	c.279_290dupGCCCGGCGTGCG	p.Arg97_Asn98insProGlyValArg	disruptive_inframe_insertion	Exon 2 of 8	5		ENSP00000461168.1
NLGN2	ENST00000570940.1	c.-111_-110insGGCCCGGCGTGC		upstream_gene_variant		3		ENSP00000461092.1
NLGN2	ENST00000572893.1	n.*23_*24insGGCCCGGCGTGC		downstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Sep 12, 2024

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Not observed at significant frequency in large population cohorts (gnomAD); In-frame duplication of 4 amino acid(s) in a non-repeat region; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Splicing

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: chr17-7311851;