Variant 2-229367096-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_139072.4(DNER):c.1879A>G(p.Met627Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000115 in 1,614,150 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000058 ( 1 hom. )

Consequence

DNER
NM_139072.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.34

Variant links:

Genes affected

DNER (HGNC:24456): (delta/notch like EGF repeat containing) Predicted to enable Notch binding activity. Involved in central nervous system development. Located in dendrite; early endosome; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

DNER links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011877686).

BP6

Variant 2-229367096-T-C is Benign according to our data. Variant chr2-229367096-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 761259.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 101 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNER	NM_139072.4 linkuse as main transcript	c.1879A>G	p.Met627Val	missense_variant	12/13	ENST00000341772.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNER	ENST00000341772.5 linkuse as main transcript	c.1879A>G	p.Met627Val	missense_variant	12/13	1	NM_139072.4	P1

Frequencies

GnomAD3 genomes

AF:

0.000664

AC:

101

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00239

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000184

AC:

AN:

249952

Hom.:

AF XY:

0.000118

AC XY:

AN XY:

135242

show subpopulations

Gnomad AFR exome

AF:

0.00283

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000581

AC:

AN:

1461840

Hom.:

Cov.:

AF XY:

0.0000468

AC XY:

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.00233

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000993

GnomAD4 genome

AF:

0.000663

AC:

101

AN:

152310

Hom.:

Cov.:

AF XY:

0.000644

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00238

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000249

Hom.:

Bravo

AF:

0.000680

ESP6500AA

AF:

0.00272

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000255

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.18

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.17

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.68

M_CAP

Benign

0.058

MetaRNN

Benign

0.012

MetaSVM

Benign

-0.63

MutationAssessor

Benign

0.0

MutationTaster

Benign

0.98

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.45

REVEL

Benign

0.25

Sift

Benign

0.33

Sift4G

Benign

0.44

Polyphen

0.0010

Vest4

0.34

MVP

0.32

MPC

0.13

ClinPred

0.027

GERP RS

4.7

Varity_R

0.24

gMVP

0.56

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