chr19-44865548-C-T

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

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

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]

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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 UniProt
NECTIN2NM_001042724.2 linkuse as main transcriptc.366C>T p.Asp122= synonymous_variant 2/9 ENST00000252483.10
NECTIN2NM_002856.3 linkuse as main transcriptc.366C>T p.Asp122= synonymous_variant 2/6
NECTIN2XM_047439169.1 linkuse as main transcriptc.366C>T p.Asp122= synonymous_variant 2/6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NECTIN2ENST00000252483.10 linkuse as main transcriptc.366C>T p.Asp122= synonymous_variant 2/91 NM_001042724.2 P3Q92692-1
NECTIN2ENST00000252485.8 linkuse as main transcriptc.366C>T p.Asp122= synonymous_variant 2/61 A2Q92692-2

Frequencies

GnomAD3 genomes
AF:
0.0159
AC:
2425
AN:
152168
Hom.:
60
Cov.:
31
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.:
21
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.:
64
Cov.:
32
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.:
60
Cov.:
31
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.:
11
Bravo
AF:
0.0175
Asia WGS
AF:
0.00289
AC:
11
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpMay 31, 2018- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

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.

Other links and lift over

dbSNP: rs34929997; hg19: chr19-45368805; API