rs35126828

Variant names:

• chr22-50518686-C-T
• rs35126828
• NM_152299.4:c.684C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_152299.4(NCAPH2):​c.684C>T​(p.Ser228Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00394 in 1,609,570 control chromosomes in the GnomAD database, including 190 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. S228S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.020 (94 hom., cov: 33)
  • Exomes 𝑓: 0.0023 (96 hom.)
• Consequence: NCAPH2 NM_152299.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.34
• Publications: 2 publications found

Genes affected

NCAPH2 (HGNC:25071): (non-SMC condensin II complex subunit H2) This gene encodes one of the non-SMC subunits of the condensin II complex. This complex plays an essential role in mitotic chromosome assembly. Alternate splicing of this gene results in multiple transcript variants.[provided by RefSeq, May 2010]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 22-50518686-C-T is Benign according to our data. Variant chr22-50518686-C-T is described in ClinVar as Benign. ClinVar VariationId is 775456.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.34 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0649 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152299.4. 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
	NCAPH2	NM_152299.4	MANE Select	c.684C>T	p.Ser228Ser	synonymous	Exon 8 of 20	NP_689512.2	Q6IBW4-1
	NCAPH2	NM_001185011.2		c.684C>T	p.Ser228Ser	synonymous	Exon 8 of 20	NP_001171940.1	Q6IBW4-4
	NCAPH2	NM_014551.5		c.684C>T	p.Ser228Ser	synonymous	Exon 8 of 9	NP_055366.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCAPH2	ENST00000420993.7	TSL:1 MANE Select	c.684C>T	p.Ser228Ser	synonymous	Exon 8 of 20	ENSP00000410088.2	Q6IBW4-1
	NCAPH2	ENST00000299821.15	TSL:1	c.684C>T	p.Ser228Ser	synonymous	Exon 8 of 20	ENSP00000299821.11	Q6IBW4-4
	NCAPH2	ENST00000395698.7	TSL:1	c.684C>T	p.Ser228Ser	synonymous	Exon 8 of 9	ENSP00000379050.3	Q6IBW4-5

Frequencies

GnomAD3 genomes AF: 0.0198 AC: 3018 AN: 152110 Hom.: 92 Cov.: 33

Gnomad AFR AF: 0.0670

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0109

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000515

Gnomad OTH AF: 0.0143

GnomAD2 exomes AF: 0.00536 AC: 1305 AN: 243658 AF XY: 0.00406

Gnomad AFR exome AF: 0.0696

Gnomad AMR exome AF: 0.00403

Gnomad ASJ exome AF: 0.00122

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000508

Gnomad OTH exome AF: 0.00435

GnomAD4 exome AF: 0.00228 AC: 3323 AN: 1457342 Hom.: 96 Cov.: 31 AF XY: 0.00203 AC XY: 1474 AN XY: 724478

African (AFR) AF: 0.0686 AC: 2292 AN: 33394

American (AMR) AF: 0.00467 AC: 207 AN: 44368

Ashkenazi Jewish (ASJ) AF: 0.00142 AC: 37 AN: 26000

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39640

South Asian (SAS) AF: 0.000129 AC: 11 AN: 85142

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52802

Middle Eastern (MID) AF: 0.00584 AC: 29 AN: 4966

European-Non Finnish (NFE) AF: 0.000365 AC: 406 AN: 1110830

Other (OTH) AF: 0.00565 AC: 340 AN: 60200

GnomAD4 genome AF: 0.0199 AC: 3024 AN: 152228 Hom.: 94 Cov.: 33 AF XY: 0.0202 AC XY: 1503 AN XY: 74414

African (AFR) AF: 0.0670 AC: 2783 AN: 41530

American (AMR) AF: 0.0109 AC: 167 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000515 AC: 35 AN: 68012

Other (OTH) AF: 0.0142 AC: 30 AN: 2116

Alfa AF: 0.0127 Hom.: 16

Bravo AF: 0.0219

Asia WGS AF: 0.00664 AC: 23 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	3.8
DANN	Benign	0.62
PhyloP100		-1.3
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs35126828; hg19: chr22-50957115;