Genetic Variant NM_014865.4:c.1955-106G>A (chr12-6522722-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014865.4(NCAPD2):c.1955-106G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 1,248,248 control chromosomes in the GnomAD database, including 22,675 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.18 ( 2619 hom., cov: 32)

Exomes 𝑓: 0.19 ( 20056 hom. )

Consequence

NCAPD2
NM_014865.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.843

Publications

11 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 Gene-Disease associations (from GenCC):

microcephaly 21, primary, autosomal recessive
Inheritance: Unknown, AR Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

NCAPD2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCAPD2	NM_014865.4 link	c.1955-106G>A		intron_variant	Intron 15 of 31	ENST00000315579.10	NP_055680.3	Q15021B3KY03B3KMS0

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
NCAPD2	ENST00000315579.10 link	c.1955-106G>A	intron_variant	Intron 15 of 31	1	NM_014865.4	ENSP00000325017.5	Q15021
NCAPD2	ENST00000382457.8 link	c.1571-106G>A	intron_variant	Intron 12 of 20	5		ENSP00000371895.4	E7EN77
NCAPD2	ENST00000538600.1 link	n.119-162G>A	intron_variant	Intron 1 of 2	3
NCAPD2	ENST00000539084.5 link	n.*1650-106G>A	intron_variant	Intron 14 of 30	2		ENSP00000438495.1	F5H431

Frequencies

GnomAD3 genomes

AF:

0.180

AC:

27362

AN:

152088

Hom.:

2617

Cov.:

show subpopulations

Gnomad AFR

AF:

0.148

Gnomad AMI

AF:

0.204

Gnomad AMR

AF:

0.201

Gnomad ASJ

AF:

0.0861

Gnomad EAS

AF:

0.335

Gnomad SAS

AF:

0.164

Gnomad FIN

AF:

0.198

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.186

Gnomad OTH

AF:

0.172

GnomAD4 exome

AF:

0.187

AC:

204461

AN:

1096042

Hom.:

20056

AF XY:

0.184

AC XY:

101506

AN XY:

550850

show subpopulations

African (AFR)

AF:

0.147

AC:

3657

AN:

24878

American (AMR)

AF:

0.205

AC:

6466

AN:

31612

Ashkenazi Jewish (ASJ)

AF:

0.0890

AC:

1697

AN:

19076

East Asian (EAS)

AF:

0.305

AC:

11465

AN:

37554

South Asian (SAS)

AF:

0.157

AC:

10358

AN:

66158

European-Finnish (FIN)

AF:

0.200

AC:

9906

AN:

49418

Middle Eastern (MID)

AF:

0.0887

AC:

426

AN:

4804

European-Non Finnish (NFE)

AF:

0.186

AC:

151849

AN:

815282

Other (OTH)

AF:

0.183

AC:

8637

AN:

47260

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

8143

16286

24428

32571

40714

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5012

10024

15036

20048

25060

<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:

0.180

AC:

27368

AN:

152206

Hom.:

2619

Cov.:

AF XY:

0.180

AC XY:

13408

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.147

AC:

6123

AN:

41516

American (AMR)

AF:

0.201

AC:

3071

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0861

AC:

299

AN:

3472

East Asian (EAS)

AF:

0.336

AC:

1737

AN:

5170

South Asian (SAS)

AF:

0.163

AC:

789

AN:

4832

European-Finnish (FIN)

AF:

0.198

AC:

2102

AN:

10594

Middle Eastern (MID)

AF:

0.0918

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.186

AC:

12675

AN:

68004

Other (OTH)

AF:

0.170

AC:

360

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1167

2335

3502

4670

5837

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

296

592

888

1184

1480

<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:

0.167

Hom.:

1438

Bravo

AF:

0.181

Asia WGS

AF:

0.251

AC:

870

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

7.3

(source)

DANN

Benign

0.73

PhyloP100

0.84

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

Computational scores

Splicing

Publications

Other links and lift over