Genetic Variant NDE1:c.-261_-258delGAAA (chr16-15643829-CAAGA-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The ENST00000674888.1(NDE1):n.-139_-136delGAAA variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000127 in 156,950 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

NDE1
ENST00000674888.1 non_coding_transcript_exon

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.525

Publications

0 publications found

Variant links:

Genes affected

NDE1 (HGNC:17619): (nudE neurodevelopment protein 1) This gene encodes a member of the nuclear distribution E (NudE) family of proteins. The encoded protein is localized at the centrosome and interacts with other centrosome components as part of a multiprotein complex that regulates dynein function. This protein plays an essential role in microtubule organization, mitosis and neuronal migration. Mutations in this gene cause lissencephaly 4, a disorder characterized by lissencephaly, severe brain atrophy, microcephaly, and severe cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2012]

NDE1 Gene-Disease associations (from GenCC):

lissencephaly 4
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: PanelApp Australia, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
hydranencephaly
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
microlissencephaly
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
NDE1-related microhydranencephaly
Inheritance: Unknown, AR Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

NDE1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
NDE1	NM_001143979.2 link	c.-261_-258delGAAA	5_prime_UTR_variant	Exon 1 of 10	NP_001137451.1	Q9NXR1-2X5DR54
NDE1	XM_006720897.5 link	c.-43_-40delGAAA	5_prime_UTR_variant	Exon 1 of 8	XP_006720960.1
NDE1	XM_047434258.1 link	c.-43_-40delGAAA	5_prime_UTR_variant	Exon 1 of 8	XP_047290214.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
NDE1	ENST00000396355.5 link	c.-261_-258delGAAA	5_prime_UTR_variant	Exon 1 of 10	1	ENSP00000379643.1	Q9NXR1-2
NDE1	ENST00000674888.1 link	n.-139_-136delGAAA	non_coding_transcript_exon_variant	Exon 1 of 10		ENSP00000501936.1	Q9NXR1-2
NDE1	ENST00000674888.1 link	n.-139_-136delGAAA	5_prime_UTR_variant	Exon 1 of 10		ENSP00000501936.1	Q9NXR1-2

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

151898

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000265

Gnomad OTH

AF:

0.000479

GnomAD4 exome

AF:

0.000198

AC:

AN:

5052

Hom.:

AF XY:

0.00

AC XY:

AN XY:

2980

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

1676

European-Finnish (FIN)

AF:

0.00

AC:

AN:

264

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.000367

AC:

AN:

2728

Other (OTH)

AF:

0.00

AC:

AN:

256

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000125

AC:

AN:

151898

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74174

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41348

American (AMR)

AF:

0.00

AC:

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10568

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000265

AC:

AN:

67970

Other (OTH)

AF:

0.000479

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000159

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Lissencephaly, Recessive

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.53

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

16-15643829-CAAGA-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over