NM_017760.7:c.3168G>A

Variant names:

• chr7-158646471-C-T
• rs192363025
• NM_017760.7:c.3168G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_017760.7(NCAPG2):​c.3168G>A​(p.Ser1056Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00246 in 1,599,408 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0016 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0026 (12 hom.)
• Consequence: NCAPG2 NM_017760.7 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -3.25
• Publications: 5 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.006).
• BP6: Variant 7-158646471-C-T is Benign according to our data. Variant chr7-158646471-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3024927.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.25 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 12 AR,Unknown gene

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.3168G>A	p.Ser1056Ser	synonymous	Exon 25 of 28	NP_060230.5
	NCAPG2	NM_001281933.2		c.3168G>A	p.Ser1056Ser	synonymous	Exon 25 of 28	NP_001268862.1	Q86XI2-2
	NCAPG2	NM_001281932.2		c.3168G>A	p.Ser1056Ser	synonymous	Exon 26 of 29	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.3168G>A	p.Ser1056Ser	synonymous	Exon 25 of 28	ENSP00000348657.3	Q86XI2-1
	NCAPG2	ENST00000409339.3	TSL:1	c.3168G>A	p.Ser1056Ser	synonymous	Exon 25 of 28	ENSP00000387007.3	Q86XI2-2
	NCAPG2	ENST00000467785.5	TSL:1	n.3012G>A		non_coding_transcript_exon	Exon 22 of 25

Frequencies

GnomAD3 genomes AF: 0.00162 AC: 246 AN: 152132 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000579

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00268

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.00159 AC: 377 AN: 236588 AF XY: 0.00180

Gnomad AFR exome AF: 0.000476

Gnomad AMR exome AF: 0.00132

Gnomad ASJ exome AF: 0.00287

Gnomad EAS exome AF: 0.0000599

Gnomad FIN exome AF: 0.000141

Gnomad NFE exome AF: 0.00238

Gnomad OTH exome AF: 0.00157

GnomAD4 exome AF: 0.00255 AC: 3696 AN: 1447158 Hom.: 12 Cov.: 29 AF XY: 0.00258 AC XY: 1858 AN XY: 720064

African (AFR) AF: 0.000372 AC: 12 AN: 32294

American (AMR) AF: 0.00118 AC: 49 AN: 41428

Ashkenazi Jewish (ASJ) AF: 0.00294 AC: 76 AN: 25882

East Asian (EAS) AF: 0.0000257 AC: 1 AN: 38934

South Asian (SAS) AF: 0.00119 AC: 100 AN: 83804

European-Finnish (FIN) AF: 0.000244 AC: 13 AN: 53182

Middle Eastern (MID) AF: 0.00174 AC: 10 AN: 5740

European-Non Finnish (NFE) AF: 0.00297 AC: 3280 AN: 1106058

Other (OTH) AF: 0.00259 AC: 155 AN: 59836

GnomAD4 genome AF: 0.00161 AC: 245 AN: 152250 Hom.: 1 Cov.: 33 AF XY: 0.00153 AC XY: 114 AN XY: 74448

African (AFR) AF: 0.000578 AC: 24 AN: 41548

American (AMR) AF: 0.00105 AC: 16 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00519 AC: 18 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4812

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00268 AC: 182 AN: 68024

Other (OTH) AF: 0.000474 AC: 1 AN: 2110

Alfa AF: 0.00248 Hom.: 0

Bravo AF: 0.00157

Asia WGS AF: 0.000289 AC: 1 AN: 3476

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	NCAPG2-related disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.040
DANN	Benign	0.30
PhyloP100		-3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs192363025; hg19: chr7-158439163; COSMIC: COSV51985499;