dbSNP rs1043262: NCAPD2:p.Val1267Val (chr12-6529922-A-G) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_014865.4(NCAPD2):c.3801A>G(p.Val1267Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.727 in 1,613,992 control chromosomes in the GnomAD database, including 428,983 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.77 ( 45947 hom., cov: 34)

Exomes 𝑓: 0.72 ( 383036 hom. )

Consequence

NCAPD2
NM_014865.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.700

Publications

26 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 12-6529922-A-G is Benign according to our data. Variant chr12-6529922-A-G is described in ClinVar as Benign. ClinVar VariationId is 1321849.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.7 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.891 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCAPD2	NM_014865.4 link	c.3801A>G	p.Val1267Val	synonymous_variant	Exon 29 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.3801A>G	p.Val1267Val	synonymous_variant	Exon 29 of 32	1	NM_014865.4	ENSP00000325017.5		Q15021

Frequencies

GnomAD3 genomes

AF:

0.772

AC:

117493

AN:

152098

Hom.:

45896

Cov.:

show subpopulations

Gnomad AFR

AF:

0.898

Gnomad AMI

AF:

0.613

Gnomad AMR

AF:

0.790

Gnomad ASJ

AF:

0.713

Gnomad EAS

AF:

0.696

Gnomad SAS

AF:

0.674

Gnomad FIN

AF:

0.756

Gnomad MID

AF:

0.693

Gnomad NFE

AF:

0.714

Gnomad OTH

AF:

0.749

GnomAD2 exomes

AF:

0.744

AC:

186921

AN:

251378

AF XY:

0.733

show subpopulations

Gnomad AFR exome

AF:

0.901

Gnomad AMR exome

AF:

0.860

Gnomad ASJ exome

AF:

0.703

Gnomad EAS exome

AF:

0.693

Gnomad FIN exome

AF:

0.753

Gnomad NFE exome

AF:

0.711

Gnomad OTH exome

AF:

0.730

GnomAD4 exome

AF:

0.723

AC:

1056491

AN:

1461776

Hom.:

383036

Cov.:

AF XY:

0.720

AC XY:

523942

AN XY:

727202

show subpopulations

African (AFR)

AF:

0.907

AC:

30360

AN:

33478

American (AMR)

AF:

0.854

AC:

38208

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.708

AC:

18488

AN:

26126

East Asian (EAS)

AF:

0.686

AC:

27217

AN:

39698

South Asian (SAS)

AF:

0.683

AC:

58884

AN:

86246

European-Finnish (FIN)

AF:

0.754

AC:

40288

AN:

53416

Middle Eastern (MID)

AF:

0.691

AC:

3986

AN:

5768

European-Non Finnish (NFE)

AF:

0.715

AC:

795136

AN:

1111942

Other (OTH)

AF:

0.727

AC:

43924

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

16930

33860

50791

67721

84651

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19962

39924

59886

79848

99810

<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:

0.773

AC:

117606

AN:

152216

Hom.:

45947

Cov.:

AF XY:

0.772

AC XY:

57471

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.898

AC:

37341

AN:

41564

American (AMR)

AF:

0.791

AC:

12096

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.713

AC:

2474

AN:

3472

East Asian (EAS)

AF:

0.697

AC:

3594

AN:

5160

South Asian (SAS)

AF:

0.674

AC:

3247

AN:

4820

European-Finnish (FIN)

AF:

0.756

AC:

8000

AN:

10586

Middle Eastern (MID)

AF:

0.677

AC:

199

AN:

294

European-Non Finnish (NFE)

AF:

0.713

AC:

48515

AN:

67996

Other (OTH)

AF:

0.749

AC:

1581

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1378

2756

4134

5512

6890

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

858

1716

2574

3432

4290

<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:

0.729

Hom.:

19541

Bravo

AF:

0.784

Asia WGS

AF:

0.766

AC:

2665

AN:

3478

EpiCase

AF:

0.705

EpiControl

AF:

0.691

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

-0.82

CADD

Benign

2.0

(source)

DANN

Benign

0.64

PhyloP100

0.70

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