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GeneBe

12-6511229-A-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_014865.4(NCAPD2):c.564A>C(p.Ser188=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0104 in 1,614,136 control chromosomes in the GnomAD database, including 197 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.011 ( 21 hom., cov: 32)
Exomes 𝑓: 0.010 ( 176 hom. )

Consequence

NCAPD2
NM_014865.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.201
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 12-6511229-A-C is Benign according to our data. Variant chr12-6511229-A-C is described in ClinVar as [Benign]. Clinvar id is 1879223.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.201 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.011 (1682/152286) while in subpopulation AMR AF= 0.00974 (149/15304). AF 95% confidence interval is 0.00868. There are 21 homozygotes in gnomad4. There are 965 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 21 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NCAPD2NM_014865.4 linkuse as main transcriptc.564A>C p.Ser188= synonymous_variant 6/32 ENST00000315579.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NCAPD2ENST00000315579.10 linkuse as main transcriptc.564A>C p.Ser188= synonymous_variant 6/321 NM_014865.4 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0111
AC:
1684
AN:
152168
Hom.:
21
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00171
Gnomad AMI
AF:
0.0581
Gnomad AMR
AF:
0.00975
Gnomad ASJ
AF:
0.0685
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00248
Gnomad FIN
AF:
0.0474
Gnomad MID
AF:
0.0411
Gnomad NFE
AF:
0.00928
Gnomad OTH
AF:
0.00717
GnomAD3 exomes
AF:
0.0118
AC:
2977
AN:
251416
Hom.:
45
AF XY:
0.0117
AC XY:
1596
AN XY:
135878
show subpopulations
Gnomad AFR exome
AF:
0.00117
Gnomad AMR exome
AF:
0.00428
Gnomad ASJ exome
AF:
0.0609
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00235
Gnomad FIN exome
AF:
0.0431
Gnomad NFE exome
AF:
0.00962
Gnomad OTH exome
AF:
0.0157
GnomAD4 exome
AF:
0.0103
AC:
15085
AN:
1461850
Hom.:
176
Cov.:
31
AF XY:
0.0102
AC XY:
7429
AN XY:
727226
show subpopulations
Gnomad4 AFR exome
AF:
0.00179
Gnomad4 AMR exome
AF:
0.00452
Gnomad4 ASJ exome
AF:
0.0613
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00224
Gnomad4 FIN exome
AF:
0.0401
Gnomad4 NFE exome
AF:
0.00896
Gnomad4 OTH exome
AF:
0.0129
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0110
AC:
1682
AN:
152286
Hom.:
21
Cov.:
32
AF XY:
0.0130
AC XY:
965
AN XY:
74444
show subpopulations
Gnomad4 AFR
AF:
0.00168
Gnomad4 AMR
AF:
0.00974
Gnomad4 ASJ
AF:
0.0685
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00249
Gnomad4 FIN
AF:
0.0474
Gnomad4 NFE
AF:
0.00928
Gnomad4 OTH
AF:
0.00710
Alfa
AF:
0.0126
Hom.:
13
Bravo
AF:
0.00749
Asia WGS
AF:
0.00289
AC:
10
AN:
3478
EpiCase
AF:
0.0108
EpiControl
AF:
0.0103

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenDec 01, 2023NCAPD2: BP4, BP7, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
Cadd
Benign
6.3
Dann
Benign
0.73
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs61753198; hg19: chr12-6620395; COSMIC: COSV59703096; COSMIC: COSV59703096; API