22-50517109-A-G

Position:

• chr22-50517109-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCAPH2	NM_152299.4	c.211-318A>G		intron_variant		ENST00000420993.7	NP_689512.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCAPH2	ENST00000420993.7	c.211-318A>G		intron_variant		1	NM_152299.4	ENSP00000410088.2

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

Gnomad4 AFR AF: 0.725

Gnomad4 AMR AF: 0.580

Gnomad4 ASJ AF: 0.575

Gnomad4 EAS AF: 0.461

Gnomad4 SAS AF: 0.628

Gnomad4 FIN AF: 0.409

Gnomad4 NFE AF: 0.571

Gnomad4 OTH AF: 0.616

Alfa AF: 0.574 Hom.: 29328

Bravo AF: 0.613

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.0
DANN	Benign	0.40

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

Publications

LitVar

Other links and lift over

dbSNP: rs131817; hg19: chr22-50955538;