dbSNP rs283814: NECTIN2:p.Pro409Pro (chr19-44885967-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001042724.2(NECTIN2):c.1227G>A(p.Pro409Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.066 in 1,602,636 control chromosomes in the GnomAD database, including 4,014 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.051 ( 277 hom., cov: 32)

Exomes 𝑓: 0.068 ( 3737 hom. )

Consequence

NECTIN2
NM_001042724.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.53

Publications

25 publications found

Variant links:

Genes affected

NECTIN2 (HGNC:9707): (nectin cell adhesion molecule 2) This gene encodes a single-pass type I membrane glycoprotein with two Ig-like C2-type domains and an Ig-like V-type domain. This protein is one of the plasma membrane components of adherens junctions. It also serves as an entry for certain mutant strains of herpes simplex virus and pseudorabies virus, and it is involved in cell to cell spreading of these viruses. Variations in this gene have been associated with differences in the severity of multiple sclerosis. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

NECTIN2 links:

ENSG00000267282 (HGNC:56209):

ENSG00000267282 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BP7

Synonymous conserved (PhyloP=-3.53 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NECTIN2	NM_001042724.2 link	c.1227G>A	p.Pro409Pro	synonymous_variant	Exon 7 of 9	ENST00000252483.10	NP_001036189.1	Q92692-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NECTIN2	ENST00000252483.10 link	c.1227G>A	p.Pro409Pro	synonymous_variant	Exon 7 of 9	1	NM_001042724.2	ENSP00000252483.4	Q92692-1
NECTIN2	ENST00000592018.1 link	c.27-2143G>A		intron_variant	Intron 1 of 1	3		ENSP00000468305.1	K7ERL3
ENSG00000267282	ENST00000585408.2 link	n.161-3629C>T		intron_variant	Intron 1 of 1	3
ENSG00000267282	ENST00000787383.1 link	n.156-3629C>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.0512

AC:

7786

AN:

152100

Hom.:

277

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0134

Gnomad AMI

AF:

0.161

Gnomad AMR

AF:

0.0655

Gnomad ASJ

AF:

0.0392

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0263

Gnomad FIN

AF:

0.0541

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0751

Gnomad OTH

AF:

0.0602

GnomAD4 exome

AF:

0.0676

AC:

98033

AN:

1450418

Hom.:

3737

Cov.:

AF XY:

0.0664

AC XY:

47973

AN XY:

722242

show subpopulations

African (AFR)

AF:

0.0119

AC:

394

AN:

33142

American (AMR)

AF:

0.0464

AC:

2074

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.0388

AC:

1013

AN:

26082

East Asian (EAS)

AF:

0.000177

AC:

AN:

39634

South Asian (SAS)

AF:

0.0289

AC:

2482

AN:

86010

European-Finnish (FIN)

AF:

0.0459

AC:

2451

AN:

53418

Middle Eastern (MID)

AF:

0.0676

AC:

389

AN:

5756

European-Non Finnish (NFE)

AF:

0.0773

AC:

85196

AN:

1101704

Other (OTH)

AF:

0.0672

AC:

4027

AN:

59962

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.541

Heterozygous variant carriers

5138

10276

15415

20553

25691

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3074

6148

9222

12296

15370

<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:

0.0512

AC:

7787

AN:

152218

Hom.:

277

Cov.:

AF XY:

0.0495

AC XY:

3687

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.0133

AC:

553

AN:

41536

American (AMR)

AF:

0.0654

AC:

1000

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0392

AC:

136

AN:

3472

East Asian (EAS)

AF:

0.000386

AC:

AN:

5182

South Asian (SAS)

AF:

0.0270

AC:

130

AN:

4822

European-Finnish (FIN)

AF:

0.0541

AC:

574

AN:

10602

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0750

AC:

5103

AN:

68006

Other (OTH)

AF:

0.0591

AC:

125

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

388

776

1164

1552

1940

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

246

328

410

<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:

0.0632

Hom.:

584

Bravo

AF:

0.0505

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.098

(source)

PhyloP100

-3.5

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over