Genetic Variant NM_001042724.2:c.89-104C>T (chr19-44865167-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.89-104C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.536 in 1,265,088 control chromosomes in the GnomAD database, including 185,777 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 0.48 ( 18858 hom., cov: 31)

Exomes 𝑓: 0.54 ( 166919 hom. )

Consequence

NECTIN2
NM_001042724.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.03

Publications

9 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:

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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=-0.94).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
NECTIN2	NM_001042724.2 link	c.89-104C>T	intron_variant	Intron 1 of 8	ENST00000252483.10	NP_001036189.1
NECTIN2	NM_002856.3 link	c.89-104C>T	intron_variant	Intron 1 of 5		NP_002847.1
NECTIN2	XM_047439169.1 link	c.89-104C>T	intron_variant	Intron 1 of 5		XP_047295125.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NECTIN2	ENST00000252483.10 link	c.89-104C>T		intron_variant	Intron 1 of 8	1	NM_001042724.2	ENSP00000252483.4
NECTIN2	ENST00000252485.8 link	c.89-104C>T		intron_variant	Intron 1 of 5	1		ENSP00000252485.3

Frequencies

GnomAD3 genomes

AF:

0.482

AC:

73199

AN:

151886

Hom.:

18856

Cov.:

show subpopulations

Gnomad AFR

AF:

0.305

Gnomad AMI

AF:

0.576

Gnomad AMR

AF:

0.412

Gnomad ASJ

AF:

0.525

Gnomad EAS

AF:

0.570

Gnomad SAS

AF:

0.471

Gnomad FIN

AF:

0.711

Gnomad MID

AF:

0.392

Gnomad NFE

AF:

0.561

Gnomad OTH

AF:

0.489

GnomAD4 exome

AF:

0.543

AC:

604699

AN:

1113084

Hom.:

166919

AF XY:

0.542

AC XY:

298341

AN XY:

550716

show subpopulations

African (AFR)

AF:

0.293

AC:

7431

AN:

25338

American (AMR)

AF:

0.369

AC:

10073

AN:

27274

Ashkenazi Jewish (ASJ)

AF:

0.532

AC:

9725

AN:

18296

East Asian (EAS)

AF:

0.557

AC:

20736

AN:

37216

South Asian (SAS)

AF:

0.460

AC:

28029

AN:

60998

European-Finnish (FIN)

AF:

0.692

AC:

33081

AN:

47776

Middle Eastern (MID)

AF:

0.433

AC:

1406

AN:

3246

European-Non Finnish (NFE)

AF:

0.555

AC:

469292

AN:

845248

Other (OTH)

AF:

0.523

AC:

24926

AN:

47692

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

13574

27147

40721

54294

67868

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12494

24988

37482

49976

62470

<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:

0.482

AC:

73216

AN:

152004

Hom.:

18858

Cov.:

AF XY:

0.489

AC XY:

36309

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.304

AC:

12622

AN:

41452

American (AMR)

AF:

0.412

AC:

6287

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.525

AC:

1822

AN:

3468

East Asian (EAS)

AF:

0.570

AC:

2934

AN:

5148

South Asian (SAS)

AF:

0.472

AC:

2274

AN:

4820

European-Finnish (FIN)

AF:

0.711

AC:

7529

AN:

10594

Middle Eastern (MID)

AF:

0.401

AC:

117

AN:

292

European-Non Finnish (NFE)

AF:

0.561

AC:

38082

AN:

67942

Other (OTH)

AF:

0.485

AC:

1024

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1847

3694

5540

7387

9234

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

650

1300

1950

2600

3250

<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:

0.527

Hom.:

11099

Bravo

AF:

0.453

Asia WGS

AF:

0.459

AC:

1597

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.18

(source)

DANN

Benign

0.52

PhyloP100

-2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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