22-50517109-A-G

Variant names:

• chr22-50517109-A-G
• rs131817
• NM_152299.4:c.211-318A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152299.4(NCAPH2):​c.211-318A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 152,010 control chromosomes in the GnomAD database, including 28,092 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.60 (28092 hom., cov: 32)
• Consequence: NCAPH2 NM_152299.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.217
• Publications: 12 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.718 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCAPH2	NM_152299.4	MANE Select	c.211-318A>G		intron	N/A	NP_689512.2
	NCAPH2	NM_001185011.2		c.211-318A>G		intron	N/A	NP_001171940.1
	NCAPH2	NM_014551.5		c.211-318A>G		intron	N/A	NP_055366.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCAPH2	ENST00000420993.7	TSL:1 MANE Select	c.211-318A>G		intron	N/A	ENSP00000410088.2
	NCAPH2	ENST00000299821.15	TSL:1	c.211-318A>G		intron	N/A	ENSP00000299821.11
	NCAPH2	ENST00000395698.7	TSL:1	c.211-318A>G		intron	N/A	ENSP00000379050.3

Frequencies

GnomAD3 genomes AF: 0.601 AC: 91242 AN: 151892 Hom.: 28049 Cov.: 32

Gnomad AFR AF: 0.725

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.581

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.462

Gnomad SAS AF: 0.627

Gnomad FIN AF: 0.409

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.612

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.601 AC: 91340 AN: 152010 Hom.: 28092 Cov.: 32 AF XY: 0.593 AC XY: 44097 AN XY: 74300

African (AFR) AF: 0.725 AC: 30077 AN: 41488

American (AMR) AF: 0.580 AC: 8866 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.575 AC: 1996 AN: 3470

East Asian (EAS) AF: 0.461 AC: 2371 AN: 5138

South Asian (SAS) AF: 0.628 AC: 3024 AN: 4818

European-Finnish (FIN) AF: 0.409 AC: 4323 AN: 10578

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.571 AC: 38790 AN: 67916

Other (OTH) AF: 0.616 AC: 1303 AN: 2116

Alfa AF: 0.580 Hom.: 42586

Bravo AF: 0.613

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.0
DANN	Benign	0.40
PhyloP100		-0.22
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: rs131817; hg19: chr22-50955538;