Genetic Variant NM_001042724.2:c.*618C>T (chr19-44888997-C-T) – 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.*618C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,328 control chromosomes in the GnomAD database, including 1,378 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 0.13 ( 1367 hom., cov: 30)

Exomes 𝑓: 0.12 ( 11 hom. )

Consequence

NECTIN2
NM_001042724.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.230

Publications

178 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=-0.82).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042724.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NECTIN2	NM_001042724.2	MANE Select	c.*618C>T		3_prime_UTR	Exon 9 of 9	NP_001036189.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NECTIN2	ENST00000252483.10	TSL:1 MANE Select	c.*618C>T	3_prime_UTR	Exon 9 of 9	ENSP00000252483.4
ENSG00000267282	ENST00000585408.2	TSL:3	n.160+1766G>A	intron	N/A
ENSG00000267282	ENST00000787383.1		n.155+1772G>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.126

AC:

19061

AN:

151368

Hom.:

1358

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0619

Gnomad AMI

AF:

0.142

Gnomad AMR

AF:

0.102

Gnomad ASJ

AF:

0.145

Gnomad EAS

AF:

0.106

Gnomad SAS

AF:

0.138

Gnomad FIN

AF:

0.190

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.161

Gnomad OTH

AF:

0.101

GnomAD4 exome

AF:

0.120

AC:

101

AN:

842

Hom.:

Cov.:

AF XY:

0.120

AC XY:

AN XY:

432

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.0980

AC:

AN:

102

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.0833

AC:

AN:

European-Finnish (FIN)

AF:

0.258

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.118

AC:

AN:

574

Other (OTH)

AF:

0.119

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.126

AC:

19099

AN:

151486

Hom.:

1367

Cov.:

AF XY:

0.128

AC XY:

9457

AN XY:

74002

show subpopulations

African (AFR)

AF:

0.0621

AC:

2568

AN:

41346

American (AMR)

AF:

0.103

AC:

1574

AN:

15228

Ashkenazi Jewish (ASJ)

AF:

0.145

AC:

501

AN:

3464

East Asian (EAS)

AF:

0.106

AC:

541

AN:

5124

South Asian (SAS)

AF:

0.137

AC:

651

AN:

4764

European-Finnish (FIN)

AF:

0.190

AC:

1985

AN:

10470

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.161

AC:

10907

AN:

67786

Other (OTH)

AF:

0.106

AC:

224

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

778

1555

2333

3110

3888

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

232

464

696

928

1160

<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:

0.124

Hom.:

874

Bravo

AF:

0.115

Asia WGS

AF:

0.180

AC:

627

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.8

(source)

DANN

Benign

0.59

PhyloP100

0.23

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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