Genetic Variant NCAPD2:p.Asn1161Asn (chr12-6528950-C-T) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_014865.4(NCAPD2):c.3483C>T(p.Asn1161Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 1,613,344 control chromosomes in the GnomAD database, including 65,096 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 9648 hom., cov: 32)

Exomes 𝑓: 0.27 ( 55448 hom. )

Consequence

NCAPD2
NM_014865.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.19

Publications

29 publications found

Variant links:

Genes affected

NCAPD2 (HGNC:24305): (non-SMC condensin I complex subunit D2) Enables histone binding activity. Involved in mitotic chromosome condensation. Located in condensed chromosome; cytosol; and nucleoplasm. Part of condensin complex. Colocalizes with cytoplasm and nuclear chromosome. Implicated in primary autosomal recessive microcephaly. [provided by Alliance of Genome Resources, Apr 2022]

NCAPD2 links:

GAPDH-DT (HGNC:55492): (GAPDH divergent transcript)

GAPDH-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 12-6528950-C-T is Benign according to our data. Variant chr12-6528950-C-T is described in ClinVar as Benign. ClinVar VariationId is 1321847.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.19 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCAPD2	NM_014865.4 link	c.3483C>T	p.Asn1161Asn	synonymous_variant	Exon 27 of 32	ENST00000315579.10	NP_055680.3	Q15021B3KY03B3KMS0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCAPD2	ENST00000315579.10 link	c.3483C>T	p.Asn1161Asn	synonymous_variant	Exon 27 of 32	1	NM_014865.4	ENSP00000325017.5		Q15021

Frequencies

GnomAD3 genomes

AF:

0.338

AC:

51373

AN:

151930

Hom.:

9633

Cov.:

show subpopulations

Gnomad AFR

AF:

0.501

Gnomad AMI

AF:

0.250

Gnomad AMR

AF:

0.354

Gnomad ASJ

AF:

0.421

Gnomad EAS

AF:

0.224

Gnomad SAS

AF:

0.252

Gnomad FIN

AF:

0.238

Gnomad MID

AF:

0.373

Gnomad NFE

AF:

0.262

Gnomad OTH

AF:

0.370

GnomAD2 exomes

AF:

0.303

AC:

76109

AN:

251430

AF XY:

0.295

show subpopulations

Gnomad AFR exome

AF:

0.509

Gnomad AMR exome

AF:

0.411

Gnomad ASJ exome

AF:

0.413

Gnomad EAS exome

AF:

0.226

Gnomad FIN exome

AF:

0.235

Gnomad NFE exome

AF:

0.268

Gnomad OTH exome

AF:

0.312

GnomAD4 exome

AF:

0.269

AC:

392959

AN:

1461296

Hom.:

55448

Cov.:

AF XY:

0.268

AC XY:

195083

AN XY:

726996

show subpopulations

African (AFR)

AF:

0.521

AC:

17443

AN:

33470

American (AMR)

AF:

0.406

AC:

18176

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.419

AC:

10954

AN:

26134

East Asian (EAS)

AF:

0.213

AC:

8468

AN:

39700

South Asian (SAS)

AF:

0.253

AC:

21834

AN:

86248

European-Finnish (FIN)

AF:

0.238

AC:

12688

AN:

53420

Middle Eastern (MID)

AF:

0.398

AC:

2285

AN:

5742

European-Non Finnish (NFE)

AF:

0.255

AC:

283338

AN:

1111482

Other (OTH)

AF:

0.294

AC:

17773

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

14251

28501

42752

57002

71253

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9678

19356

29034

38712

48390

<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:

0.338

AC:

51425

AN:

152048

Hom.:

9648

Cov.:

AF XY:

0.336

AC XY:

24980

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.501

AC:

20760

AN:

41450

American (AMR)

AF:

0.354

AC:

5416

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.421

AC:

1461

AN:

3468

East Asian (EAS)

AF:

0.224

AC:

1155

AN:

5160

South Asian (SAS)

AF:

0.253

AC:

1220

AN:

4820

European-Finnish (FIN)

AF:

0.238

AC:

2517

AN:

10584

Middle Eastern (MID)

AF:

0.356

AC:

104

AN:

292

European-Non Finnish (NFE)

AF:

0.262

AC:

17792

AN:

67970

Other (OTH)

AF:

0.366

AC:

772

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1663

3326

4989

6652

8315

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

484

968

1452

1936

2420

<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:

0.312

Hom.:

6403

Bravo

AF:

0.358

Asia WGS

AF:

0.279

AC:

973

AN:

3478

EpiCase

AF:

0.290

EpiControl

AF:

0.287

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Microcephaly 21, primary, autosomal recessive

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

5.9

(source)

DANN

Benign

0.85

PhyloP100

-1.2

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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.

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