Variant 19-44865548-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001042724.2(NECTIN2):c.366C>T(p.Asp122=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0031 in 1,569,090 control chromosomes in the GnomAD database, including 124 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 60 hom., cov: 31)

Exomes 𝑓: 0.0017 ( 64 hom. )

Consequence

NECTIN2
NM_001042724.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -6.15

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 made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 19-44865548-C-T is Benign according to our data. Variant chr19-44865548-C-T is described in ClinVar as [Benign]. Clinvar id is 781489.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-6.15 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.054 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
NECTIN2	NM_001042724.2 linkuse as main transcript	c.366C>T	p.Asp122=	synonymous_variant	2/9	ENST00000252483.10
NECTIN2	NM_002856.3 linkuse as main transcript	c.366C>T	p.Asp122=	synonymous_variant	2/6
NECTIN2	XM_047439169.1 linkuse as main transcript	c.366C>T	p.Asp122=	synonymous_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NECTIN2	ENST00000252483.10 linkuse as main transcript	c.366C>T	p.Asp122=	synonymous_variant	2/9	1	NM_001042724.2	P3	Q92692-1
NECTIN2	ENST00000252485.8 linkuse as main transcript	c.366C>T	p.Asp122=	synonymous_variant	2/6	1		A2	Q92692-2

Frequencies

GnomAD3 genomes

AF:

0.0159

AC:

2425

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0560

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.00956

GnomAD3 exomes

AF:

0.00402

AC:

714

AN:

177630

Hom.:

AF XY:

0.00301

AC XY:

287

AN XY:

95334

show subpopulations

Gnomad AFR exome

AF:

0.0591

Gnomad AMR exome

AF:

0.00180

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000319

Gnomad FIN exome

AF:

0.000144

Gnomad NFE exome

AF:

0.000375

Gnomad OTH exome

AF:

0.00145

GnomAD4 exome

AF:

0.00172

AC:

2435

AN:

1416804

Hom.:

Cov.:

AF XY:

0.00146

AC XY:

1021

AN XY:

701398

show subpopulations

Gnomad4 AFR exome

AF:

0.0586

Gnomad4 AMR exome

AF:

0.00215

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000810

Gnomad4 SAS exome

AF:

0.000220

Gnomad4 FIN exome

AF:

0.0000212

Gnomad4 NFE exome

AF:

0.000211

Gnomad4 OTH exome

AF:

0.00342

GnomAD4 genome

AF:

0.0159

AC:

2428

AN:

152286

Hom.:

Cov.:

AF XY:

0.0156

AC XY:

1162

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0559

Gnomad4 AMR

AF:

0.00392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.00946

Alfa

AF:

0.00401

Hom.:

Bravo

AF:

0.0175

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.32

DANN

Benign

0.41

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over