Genetic Variant NM_001042724.2:c.1347+120G>A (chr19-44886339-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001042724.2(NECTIN2):c.1347+120G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0423 in 781,942 control chromosomes in the GnomAD database, including 1,039 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 0.063 ( 482 hom., cov: 32)

Exomes 𝑓: 0.037 ( 557 hom. )

Consequence

NECTIN2
NM_001042724.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00100

Publications

50 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NECTIN2	NM_001042724.2 link	c.1347+120G>A		intron_variant	Intron 8 of 8	ENST00000252483.10	NP_001036189.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
NECTIN2	ENST00000252483.10 link	c.1347+120G>A	intron_variant	Intron 8 of 8	1	NM_001042724.2	ENSP00000252483.4
NECTIN2	ENST00000592018.1 link	c.27-1771G>A	intron_variant	Intron 1 of 1	3		ENSP00000468305.1
ENSG00000267282	ENST00000585408.2 link	n.161-4001C>T	intron_variant	Intron 1 of 1	3
ENSG00000267282	ENST00000787383.1 link	n.156-4001C>T	intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.0625

AC:

9515

AN:

152136

Hom.:

482

Cov.:

show subpopulations

Gnomad AFR

AF:

0.132

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.0331

Gnomad ASJ

AF:

0.0493

Gnomad EAS

AF:

0.0707

Gnomad SAS

AF:

0.0447

Gnomad FIN

AF:

0.0164

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0361

Gnomad OTH

AF:

0.0622

GnomAD4 exome

AF:

0.0374

AC:

23552

AN:

629688

Hom.:

557

AF XY:

0.0374

AC XY:

12159

AN XY:

325498

show subpopulations

African (AFR)

AF:

0.133

AC:

2183

AN:

16438

American (AMR)

AF:

0.0238

AC:

559

AN:

23456

Ashkenazi Jewish (ASJ)

AF:

0.0599

AC:

928

AN:

15500

East Asian (EAS)

AF:

0.0551

AC:

1827

AN:

33134

South Asian (SAS)

AF:

0.0414

AC:

2237

AN:

54076

European-Finnish (FIN)

AF:

0.0213

AC:

750

AN:

35208

Middle Eastern (MID)

AF:

0.0464

AC:

108

AN:

2326

European-Non Finnish (NFE)

AF:

0.0327

AC:

13659

AN:

417546

Other (OTH)

AF:

0.0407

AC:

1301

AN:

32004

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1104

2208

3312

4416

5520

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

290

580

870

1160

1450

<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:

0.0625

AC:

9519

AN:

152254

Hom.:

482

Cov.:

AF XY:

0.0616

AC XY:

4588

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.132

AC:

5483

AN:

41512

American (AMR)

AF:

0.0330

AC:

505

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0493

AC:

171

AN:

3472

East Asian (EAS)

AF:

0.0708

AC:

367

AN:

5180

South Asian (SAS)

AF:

0.0442

AC:

213

AN:

4824

European-Finnish (FIN)

AF:

0.0164

AC:

174

AN:

10618

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0361

AC:

2454

AN:

68024

Other (OTH)

AF:

0.0634

AC:

134

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

448

896

1343

1791

2239

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

196

294

392

490

<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:

0.0467

Hom.:

498

Bravo

AF:

0.0659

Asia WGS

AF:

0.0710

AC:

247

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

8.5

(source)

DANN

Benign

0.76

PhyloP100

-0.0010

Mutation Taster

=100/0

polymorphism (auto)

(source)

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