Genetic Variant NLGN2:p.Thr76Thr (chr17-7408483-G-A) – ACMG Classification: Benign (-18 pts)

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_020795.4(NLGN2):c.228G>A(p.Thr76Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00095 in 1,510,344 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0047 ( 6 hom., cov: 31)

Exomes 𝑓: 0.00053 ( 8 hom. )

Consequence

NLGN2
NM_020795.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.18

Publications

1 publications found

Variant links:

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]

NLGN2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 17-7408483-G-A is Benign according to our data. Variant chr17-7408483-G-A is described in ClinVar as Benign. ClinVar VariationId is 790175.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00472 (715/151600) while in subpopulation AFR AF = 0.0165 (684/41428). AF 95% confidence interval is 0.0155. There are 6 homozygotes in GnomAd4. There are 324 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High AC in GnomAd4 at 715 AD gene.

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.228G>A	p.Thr76Thr	synonymous	Exon 1 of 7	NP_065846.1	Q8NFZ4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NLGN2	ENST00000302926.7	TSL:1 MANE Select	c.228G>A	p.Thr76Thr	synonymous	Exon 1 of 7	ENSP00000305288.2	Q8NFZ4
NLGN2	ENST00000575301.5	TSL:5	c.228G>A	p.Thr76Thr	synonymous	Exon 2 of 8	ENSP00000461168.1	Q8NFZ4
NLGN2	ENST00000572893.1	TSL:3	n.279G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.00462

AC:

700

AN:

151492

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0162

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.0000295

Gnomad OTH

AF:

0.00385

GnomAD2 exomes

AF:

0.000746

AC:

AN:

120700

AF XY:

0.000348

show subpopulations

Gnomad AFR exome

AF:

0.0223

Gnomad AMR exome

AF:

0.000943

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000976

Gnomad OTH exome

AF:

0.000640

GnomAD4 exome

AF:

0.000530

AC:

720

AN:

1358744

Hom.:

Cov.:

AF XY:

0.000434

AC XY:

292

AN XY:

672982

show subpopulations

African (AFR)

AF:

0.0209

AC:

570

AN:

27286

American (AMR)

AF:

0.00107

AC:

AN:

31644

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23394

East Asian (EAS)

AF:

0.00

AC:

AN:

31032

South Asian (SAS)

AF:

0.0000795

AC:

AN:

75454

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42824

Middle Eastern (MID)

AF:

0.00156

AC:

AN:

4500

European-Non Finnish (NFE)

AF:

0.0000187

AC:

AN:

1066990

Other (OTH)

AF:

0.00149

AC:

AN:

55620

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.527

Heterozygous variant carriers

101

134

168

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00472

AC:

715

AN:

151600

Hom.:

Cov.:

AF XY:

0.00437

AC XY:

324

AN XY:

74106

show subpopulations

African (AFR)

AF:

0.0165

AC:

684

AN:

41428

American (AMR)

AF:

0.00131

AC:

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10442

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000295

AC:

AN:

67714

Other (OTH)

AF:

0.00381

AC:

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

103

138

172

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00469

Hom.:

Bravo

AF:

0.00528

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

8.0

(source)

DANN

Benign

0.96

PhyloP100

-3.2

PromoterAI

0.042

Neutral

(source)

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over