Genetic Variant NDN:p.Asp286Asp (chr15-23686360-G-A) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_002487.3(NDN):c.858C>T(p.Asp286Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 1,595,954 control chromosomes in the GnomAD database, including 36,678 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.17 ( 2925 hom., cov: 32)

Exomes 𝑓: 0.21 ( 33753 hom. )

Consequence

NDN
NM_002487.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.354

Publications

23 publications found

Variant links:

Genes affected

NDN (HGNC:7675): (necdin, MAGE family member) This intronless gene is located in the Prader-Willi syndrome deletion region. It is an imprinted gene and is expressed exclusively from the paternal allele. Studies in mouse suggest that the protein encoded by this gene may suppress growth in postmitotic neurons. [provided by RefSeq, Jul 2008]

NDN links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 15-23686360-G-A is Benign according to our data. Variant chr15-23686360-G-A is described in ClinVar as Benign. ClinVar VariationId is 2796505.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.354 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDN	NM_002487.3 link	c.858C>T	p.Asp286Asp	synonymous_variant	Exon 1 of 1	ENST00000649030.2	NP_002478.1	Q99608X5D982

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDN	ENST00000649030.2 link	c.858C>T	p.Asp286Asp	synonymous_variant	Exon 1 of 1		NM_002487.3	ENSP00000497916.1		Q99608

Frequencies

GnomAD3 genomes

AF:

0.174

AC:

26484

AN:

151944

Hom.:

2923

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0418

Gnomad AMI

AF:

0.222

Gnomad AMR

AF:

0.291

Gnomad ASJ

AF:

0.253

Gnomad EAS

AF:

0.368

Gnomad SAS

AF:

0.185

Gnomad FIN

AF:

0.179

Gnomad MID

AF:

0.278

Gnomad NFE

AF:

0.207

Gnomad OTH

AF:

0.186

GnomAD2 exomes

AF:

0.222

AC:

52973

AN:

238980

AF XY:

0.219

show subpopulations

Gnomad AFR exome

AF:

0.0391

Gnomad AMR exome

AF:

0.295

Gnomad ASJ exome

AF:

0.248

Gnomad EAS exome

AF:

0.385

Gnomad FIN exome

AF:

0.182

Gnomad NFE exome

AF:

0.213

Gnomad OTH exome

AF:

0.218

GnomAD4 exome

AF:

0.211

AC:

304210

AN:

1443894

Hom.:

33753

Cov.:

AF XY:

0.210

AC XY:

150468

AN XY:

716100

show subpopulations

African (AFR)

AF:

0.0333

AC:

1095

AN:

32884

American (AMR)

AF:

0.294

AC:

12641

AN:

43008

Ashkenazi Jewish (ASJ)

AF:

0.254

AC:

6352

AN:

25050

East Asian (EAS)

AF:

0.360

AC:

14209

AN:

39468

South Asian (SAS)

AF:

0.191

AC:

15981

AN:

83758

European-Finnish (FIN)

AF:

0.190

AC:

9972

AN:

52554

Middle Eastern (MID)

AF:

0.242

AC:

1254

AN:

5182

European-Non Finnish (NFE)

AF:

0.209

AC:

230197

AN:

1102518

Other (OTH)

AF:

0.210

AC:

12509

AN:

59472

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

14687

29374

44061

58748

73435

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8086

16172

24258

32344

40430

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.174

AC:

26486

AN:

152060

Hom.:

2925

Cov.:

AF XY:

0.177

AC XY:

13124

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.0417

AC:

1731

AN:

41532

American (AMR)

AF:

0.291

AC:

4455

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.253

AC:

879

AN:

3472

East Asian (EAS)

AF:

0.369

AC:

1892

AN:

5126

South Asian (SAS)

AF:

0.184

AC:

882

AN:

4802

European-Finnish (FIN)

AF:

0.179

AC:

1888

AN:

10576

Middle Eastern (MID)

AF:

0.289

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.207

AC:

14081

AN:

67958

Other (OTH)

AF:

0.185

AC:

391

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1070

2140

3209

4279

5349

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

288

576

864

1152

1440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.158

Hom.:

864

Bravo

AF:

0.177

Asia WGS

AF:

0.233

AC:

812

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 02, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

9.3

(source)

DANN

Benign

0.66

PhyloP100

0.35

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over