chr19-44878340-T-TGAG

Position:

• chr19-44878340-T-TGAG

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP3 BP6 BS2

The ENST00000252485.8(NECTIN2):​c.1172_1174dup​(p.Arg391dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00359 in 1,534,678 control chromosomes in the GnomAD database, including 7 homozygotes. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0022 (1 hom., cov: 30)
  • Exomes 𝑓: 0.0037 (6 hom.)
• Consequence: NECTIN2 ENST00000252485.8 inframe_insertion
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.91

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 Likely_benign. Variant got -6 ACMG points.

• BP3: Nonframeshift variant in repetitive region in ENST00000252485.8
• BP6: Variant 19-44878340-T-TGAG is Benign according to our data. Variant chr19-44878340-T-TGAG is described in ClinVar as [Likely_benign]. Clinvar id is 3034381.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NECTIN2	NM_001042724.2	c.1043-3859_1043-3857dup		intron_variant		ENST00000252483.10	NP_001036189.1
NECTIN2	NM_002856.3	c.1172_1174dup	p.Arg391dup	inframe_insertion	6/6		NP_002847.1
NECTIN2	XM_047439169.1	c.1043-201_1043-199dup		intron_variant			XP_047295125.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NECTIN2	ENST00000252485.8	c.1172_1174dup	p.Arg391dup	inframe_insertion	6/6	1		ENSP00000252485	A2
NECTIN2	ENST00000252483.10	c.1043-3859_1043-3857dup		intron_variant		1	NM_001042724.2	ENSP00000252483	P3
NECTIN2	ENST00000585601.1	c.85-21_85-19dup		intron_variant		3		ENSP00000465511
NECTIN2	ENST00000591581.1	c.565-201_565-199dup		intron_variant		2		ENSP00000465587

Frequencies

GnomAD3 genomes AF: 0.00225 AC: 336 AN: 149436 Hom.: 1 Cov.: 30

Gnomad AFR AF: 0.000767

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00167

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00171

Gnomad FIN AF: 0.0000977

Gnomad MID AF: 0.00321

Gnomad NFE AF: 0.00396

Gnomad OTH AF: 0.00147

GnomAD3 exomes AF: 0.00188 AC: 264 AN: 140176 Hom.: 0 AF XY: 0.00184 AC XY: 135 AN XY: 73464

Gnomad AFR exome AF: 0.000857

Gnomad AMR exome AF: 0.000907

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00103

Gnomad FIN exome AF: 0.000283

Gnomad NFE exome AF: 0.00391

Gnomad OTH exome AF: 0.00149

GnomAD4 exome AF: 0.00373 AC: 5171 AN: 1385130 Hom.: 6 Cov.: 30 AF XY: 0.00369 AC XY: 2523 AN XY: 683746

Gnomad4 AFR exome AF: 0.000639

Gnomad4 AMR exome AF: 0.00129

Gnomad4 ASJ exome AF: 0.0000803

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00122

Gnomad4 FIN exome AF: 0.000326

Gnomad4 NFE exome AF: 0.00457

Gnomad4 OTH exome AF: 0.00205

GnomAD4 genome AF: 0.00225 AC: 336 AN: 149548 Hom.: 1 Cov.: 30 AF XY: 0.00207 AC XY: 151 AN XY: 73004

Gnomad4 AFR AF: 0.000765

Gnomad4 AMR AF: 0.00167

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00172

Gnomad4 FIN AF: 0.0000977

Gnomad4 NFE AF: 0.00396

Gnomad4 OTH AF: 0.00145

Bravo AF: 0.00207

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

NECTIN2-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 26, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs375813744; hg19: chr19-45381597;