rs745722598

Variant names:

• chr19-44871836-TCTC-T
• rs745722598
• NM_001042724.2:c.479-10_479-8delCTC

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP6

The NM_001042724.2(NECTIN2):​c.479-10_479-8delCTC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000339 in 1,607,238 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00023 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00035 (0 hom.)
• Consequence: NECTIN2 NM_001042724.2 splice_region, intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.170
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP6: Variant 19-44871836-TCTC-T is Benign according to our data. Variant chr19-44871836-TCTC-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3041222.Status of the report is no_assertion_criteria_provided, 0 stars.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NECTIN2	NM_001042724.2	MANE Select	c.479-10_479-8delCTC		splice_region intron	N/A	NP_001036189.1	Q92692-1
	NECTIN2	NM_002856.3		c.479-10_479-8delCTC		splice_region intron	N/A	NP_002847.1	Q92692-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NECTIN2	ENST00000252483.10	TSL:1 MANE Select	c.479-16_479-14delCTC		intron	N/A	ENSP00000252483.4	Q92692-1
	NECTIN2	ENST00000252485.8	TSL:1	c.479-16_479-14delCTC		intron	N/A	ENSP00000252485.3	Q92692-2
	NECTIN2	ENST00000883539.1		c.620-16_620-14delCTC		intron	N/A	ENSP00000553598.1

Frequencies

GnomAD3 genomes AF: 0.000230 AC: 35 AN: 151896 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000726

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

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: 0.000441

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.000219 AC: 54 AN: 246500 AF XY: 0.000254

Gnomad AFR exome AF: 0.000189

Gnomad AMR exome AF: 0.0000291

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000445

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.000350 AC: 510 AN: 1455224 Hom.: 0 AF XY: 0.000325 AC XY: 235 AN XY: 722520

African (AFR) AF: 0.000180 AC: 6 AN: 33328

American (AMR) AF: 0.0000899 AC: 4 AN: 44512

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25978

East Asian (EAS) AF: 0.00 AC: 0 AN: 39490

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86068

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53306

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5690

European-Non Finnish (NFE) AF: 0.000435 AC: 481 AN: 1106784

Other (OTH) AF: 0.000283 AC: 17 AN: 60068

GnomAD4 genome AF: 0.000230 AC: 35 AN: 152014 Hom.: 0 Cov.: 31 AF XY: 0.000188 AC XY: 14 AN XY: 74306

African (AFR) AF: 0.0000724 AC: 3 AN: 41448

American (AMR) AF: 0.0000655 AC: 1 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10582

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000441 AC: 30 AN: 67972

Other (OTH) AF: 0.000474 AC: 1 AN: 2110

Alfa AF: 0.000214 Hom.: 0

Bravo AF: 0.000219

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	NECTIN2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.17
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs745722598; hg19: chr19-45375093;