12-6510118-C-G

Variant names:

• chr12-6510118-C-G
• rs714774
• NM_014865.4:c.247C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014865.4(NCAPD2):​c.247C>G​(p.Gln83Glu) variant causes a missense change. The variant allele was found at a frequency of 0.738 in 1,608,940 control chromosomes in the GnomAD database, including 441,391 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.79 (48494 hom., cov: 32)
  • Exomes 𝑓: 0.73 (392897 hom.)
• Consequence: NCAPD2 NM_014865.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 4.83
• Publications: 40 publications found

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]

SCARNA10 (HGNC:32567): (small Cajal body-specific RNA 10)

ENSG00000276232 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.7810513E-7).
• BP6: Variant 12-6510118-C-G is Benign according to our data. Variant chr12-6510118-C-G is described in ClinVar as Benign. ClinVar VariationId is 1321844.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014865.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCAPD2	NM_014865.4	MANE Select	c.247C>G	p.Gln83Glu	missense	Exon 4 of 32	NP_055680.3
	SCARNA10	NR_004387.1		n.-104C>G		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCAPD2	ENST00000315579.10	TSL:1 MANE Select	c.247C>G	p.Gln83Glu	missense	Exon 4 of 32	ENSP00000325017.5	Q15021
	NCAPD2	ENST00000925386.1		c.370C>G	p.Gln124Glu	missense	Exon 5 of 33	ENSP00000595445.1
	NCAPD2	ENST00000925383.1		c.247C>G	p.Gln83Glu	missense	Exon 4 of 32	ENSP00000595442.1

Frequencies

GnomAD3 genomes AF: 0.792 AC: 120398 AN: 152044 Hom.: 48437 Cov.: 32

Gnomad AFR AF: 0.947

Gnomad AMI AF: 0.639

Gnomad AMR AF: 0.803

Gnomad ASJ AF: 0.720

Gnomad EAS AF: 0.667

Gnomad SAS AF: 0.685

Gnomad FIN AF: 0.765

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.723

Gnomad OTH AF: 0.767

GnomAD2 exomes AF: 0.753 AC: 189024 AN: 251158 AF XY: 0.742

Gnomad AFR exome AF: 0.952

Gnomad AMR exome AF: 0.866

Gnomad ASJ exome AF: 0.712

Gnomad EAS exome AF: 0.653

Gnomad FIN exome AF: 0.762

Gnomad NFE exome AF: 0.723

Gnomad OTH exome AF: 0.740

GnomAD4 exome AF: 0.733 AC: 1067489 AN: 1456776 Hom.: 392897 Cov.: 43 AF XY: 0.731 AC XY: 529596 AN XY: 724966

African (AFR) AF: 0.957 AC: 31945 AN: 33376

American (AMR) AF: 0.861 AC: 38509 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.715 AC: 18659 AN: 26098

East Asian (EAS) AF: 0.654 AC: 25951 AN: 39688

South Asian (SAS) AF: 0.691 AC: 59562 AN: 86148

European-Finnish (FIN) AF: 0.765 AC: 40865 AN: 53406

Middle Eastern (MID) AF: 0.706 AC: 4065 AN: 5758

European-Non Finnish (NFE) AF: 0.726 AC: 803454 AN: 1107336

Other (OTH) AF: 0.738 AC: 44479 AN: 60260

GnomAD4 genome AF: 0.792 AC: 120517 AN: 152164 Hom.: 48494 Cov.: 32 AF XY: 0.792 AC XY: 58886 AN XY: 74390

African (AFR) AF: 0.947 AC: 39340 AN: 41550

American (AMR) AF: 0.803 AC: 12263 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.720 AC: 2500 AN: 3470

East Asian (EAS) AF: 0.667 AC: 3458 AN: 5182

South Asian (SAS) AF: 0.684 AC: 3297 AN: 4818

European-Finnish (FIN) AF: 0.765 AC: 8089 AN: 10570

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.723 AC: 49166 AN: 67982

Other (OTH) AF: 0.766 AC: 1617 AN: 2110

Alfa AF: 0.723 Hom.: 27316

Bravo AF: 0.805

TwinsUK AF: 0.735 AC: 2724

ALSPAC AF: 0.729 AC: 2809

ESP6500AA AF: 0.943 AC: 4154

ESP6500EA AF: 0.716 AC: 6159

ExAC AF: 0.753 AC: 91465

Asia WGS AF: 0.768 AC: 2672 AN: 3478

EpiCase AF: 0.713

EpiControl AF: 0.703

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Microcephaly 21, primary, autosomal recessive (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.038
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	19
DANN	Benign	0.77
DEOGEN2	Benign	0.0092	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.15	T
MetaRNN	Benign	5.8e-7	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-2.2	N
PhyloP100		4.8
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	0.96	N
REVEL	Benign	0.13
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.021
MPC		0.20
ClinPred		0.0086	T
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.18
gMVP		0.12
Mutation Taster		=94/6	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs714774; hg19: chr12-6619284; COSMIC: COSV59701989; COSMIC: COSV59701989;