19-44865548-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -6.15

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]

ACMG classification

Verdict is Benign. Variant got -15 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_single_submitter, 1 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	UniProt
NECTIN2	NM_001042724.2	c.366C>T	p.Asp122=	synonymous_variant	2/9	ENST00000252483.10
NECTIN2	NM_002856.3	c.366C>T	p.Asp122=	synonymous_variant	2/6
NECTIN2	XM_047439169.1	c.366C>T	p.Asp122=	synonymous_variant	2/6

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0159 AC: 2425 AN: 152168 Hom.: 60 Cov.: 31

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.: 21 AF XY: 0.00301 AC XY: 287 AN XY: 95334

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.: 64 Cov.: 32 AF XY: 0.00146 AC XY: 1021 AN XY: 701398

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.: 60 Cov.: 31 AF XY: 0.0156 AC XY: 1162 AN XY: 74478

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.: 11

Bravo AF: 0.0175

Asia WGS AF: 0.00289 AC: 11 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 31, 2018

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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

Other links and lift over

dbSNP: rs34929997; hg19: chr19-45368805;