chr7-158652283-T-G

Variant names:

• chr7-158652283-T-G
• rs1466210
• NM_017760.7:c.2934+10A>C

Variant summary

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

The NM_017760.7(NCAPG2):​c.2934+10A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 1,610,884 control chromosomes in the GnomAD database, including 424,198 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.74 (42067 hom., cov: 33)
  • Exomes 𝑓: 0.72 (382131 hom.)
• Consequence: NCAPG2 NM_017760.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.40
• Publications: 14 publications found

Genes affected

NCAPG2 (HGNC:21904): (non-SMC condensin II complex subunit G2) This gene encodes a protein that belongs to the Condensin2nSMC family of proteins. The encoded protein is a regulatory subunit of the condensin II complex which, along with the condensin I complex, plays a role in chromosome assembly and segregation during mitosis. A similar protein in mouse is required for early development of the embryo. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

NCAPG2 Gene-Disease associations (from GenCC):

• Khan-Khan-Katsanis syndrome

  Inheritance: AR, Unknown Classification: LIMITED Submitted by: Illumina, Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 7-158652283-T-G is Benign according to our data. Variant chr7-158652283-T-G is described in ClinVar as Benign. ClinVar VariationId is 1321855.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.946 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017760.7. 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
	NCAPG2	NM_017760.7	MANE Select	c.2934+10A>C		intron	N/A	NP_060230.5
	NCAPG2	NM_001281933.2		c.2934+10A>C		intron	N/A	NP_001268862.1	Q86XI2-2
	NCAPG2	NM_001281932.2		c.2934+10A>C		intron	N/A	NP_001268861.1	Q86XI2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCAPG2	ENST00000356309.8	TSL:1 MANE Select	c.2934+10A>C		intron	N/A	ENSP00000348657.3	Q86XI2-1
	NCAPG2	ENST00000409339.3	TSL:1	c.2934+10A>C		intron	N/A	ENSP00000387007.3	Q86XI2-2
	NCAPG2	ENST00000467785.5	TSL:1	n.2778+10A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.741 AC: 112681 AN: 152022 Hom.: 42028 Cov.: 33

Gnomad AFR AF: 0.758

Gnomad AMI AF: 0.656

Gnomad AMR AF: 0.775

Gnomad ASJ AF: 0.687

Gnomad EAS AF: 0.969

Gnomad SAS AF: 0.783

Gnomad FIN AF: 0.806

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.719

GnomAD2 exomes AF: 0.754 AC: 186327 AN: 247010 AF XY: 0.751

Gnomad AFR exome AF: 0.758

Gnomad AMR exome AF: 0.789

Gnomad ASJ exome AF: 0.713

Gnomad EAS exome AF: 0.973

Gnomad FIN exome AF: 0.801

Gnomad NFE exome AF: 0.699

Gnomad OTH exome AF: 0.734

GnomAD4 exome AF: 0.722 AC: 1052920 AN: 1458744 Hom.: 382131 Cov.: 43 AF XY: 0.723 AC XY: 524412 AN XY: 725722

African (AFR) AF: 0.751 AC: 25023 AN: 33330

American (AMR) AF: 0.784 AC: 34347 AN: 43784

Ashkenazi Jewish (ASJ) AF: 0.706 AC: 18415 AN: 26076

East Asian (EAS) AF: 0.962 AC: 38155 AN: 39672

South Asian (SAS) AF: 0.771 AC: 66025 AN: 85596

European-Finnish (FIN) AF: 0.797 AC: 42499 AN: 53340

Middle Eastern (MID) AF: 0.691 AC: 3979 AN: 5756

European-Non Finnish (NFE) AF: 0.702 AC: 780153 AN: 1110912

Other (OTH) AF: 0.735 AC: 44324 AN: 60278

GnomAD4 genome AF: 0.741 AC: 112775 AN: 152140 Hom.: 42067 Cov.: 33 AF XY: 0.748 AC XY: 55658 AN XY: 74416

African (AFR) AF: 0.758 AC: 31453 AN: 41478

American (AMR) AF: 0.776 AC: 11853 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.687 AC: 2384 AN: 3468

East Asian (EAS) AF: 0.969 AC: 5025 AN: 5188

South Asian (SAS) AF: 0.783 AC: 3776 AN: 4824

European-Finnish (FIN) AF: 0.806 AC: 8540 AN: 10598

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.698 AC: 47419 AN: 67982

Other (OTH) AF: 0.723 AC: 1530 AN: 2116

Alfa AF: 0.715 Hom.: 160229

Bravo AF: 0.742

Asia WGS AF: 0.847 AC: 2946 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Khan-Khan-Katsanis syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.49
DANN	Benign	0.33
PhyloP100		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1466210; hg19: chr7-158444975;