Variant chr2-229367103-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_139072.4(DNER):c.1872C>T(p.Ser624=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00164 in 1,614,048 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0017 ( 3 hom. )

Consequence

DNER
NM_139072.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.91

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 2-229367103-G-A is Benign according to our data. Variant chr2-229367103-G-A is described in ClinVar as [Benign]. Clinvar id is 723034.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.91 with no splicing effect.

BS2

High AC in GnomAd4 at 227 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNER	NM_139072.4 linkuse as main transcript	c.1872C>T	p.Ser624=	synonymous_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.1872C>T	p.Ser624=	synonymous_variant	12/13	1	NM_139072.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00150

AC:

228

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00240

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00139

AC:

348

AN:

249690

Hom.:

AF XY:

0.00147

AC XY:

198

AN XY:

135104

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.000463

Gnomad ASJ exome

AF:

0.00497

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.000719

Gnomad FIN exome

AF:

0.000648

Gnomad NFE exome

AF:

0.00200

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.00166

AC:

2425

AN:

1461814

Hom.:

Cov.:

AF XY:

0.00165

AC XY:

1198

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.000538

Gnomad4 AMR exome

AF:

0.000626

Gnomad4 ASJ exome

AF:

0.00417

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.000812

Gnomad4 FIN exome

AF:

0.000674

Gnomad4 NFE exome

AF:

0.00185

Gnomad4 OTH exome

AF:

0.00172

GnomAD4 genome

AF:

0.00149

AC:

227

AN:

152234

Hom.:

Cov.:

AF XY:

0.00134

AC XY:

100

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.000943

Gnomad4 NFE

AF:

0.00240

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00192

Hom.:

Bravo

AF:

0.00155

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00267

EpiControl

AF:

0.00249

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.41

DANN

Benign

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