17-79779446-C-CTG

Position:

• chr17-79779446-C-CTG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_005189.3(CBX2):​c.182+20_182+21dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 1,608,050 control chromosomes in the GnomAD database, including 61,198 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.28 (5986 hom., cov: 21)
  • Exomes 𝑓: 0.27 (55212 hom.)
• Consequence: CBX2 NM_005189.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.47

Genes affected

CBX2 (HGNC:1552): (chromobox 2) This gene encodes a component of the polycomb multiprotein complex, which is required to maintain the transcriptionally repressive state of many genes throughout development via chromatin remodeling and modification of histones. Disruption of this gene in mice results in male-to-female gonadal sex reversal. Mutations in this gene are also associated with gonadal dysgenesis in humans. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene.[provided by RefSeq, Mar 2010]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 17-79779446-C-CTG is Benign according to our data. Variant chr17-79779446-C-CTG is described in ClinVar as [Benign]. Clinvar id is 1601133.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CBX2	NM_005189.3	c.182+20_182+21dup		intron_variant		ENST00000310942.9	NP_005180.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CBX2	ENST00000310942.9	c.182+20_182+21dup		intron_variant		1	NM_005189.3	ENSP00000308750	P1
CBX2	ENST00000269399.5	c.182+20_182+21dup		intron_variant		1		ENSP00000269399
CBX2	ENST00000571484.1	n.275_276dup		non_coding_transcript_exon_variant	3/3	1

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41901 AN: 151736 Hom.: 5984 Cov.: 21

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.257

GnomAD3 exomes AF: 0.248 AC: 61273 AN: 247204 Hom.: 8141 AF XY: 0.255 AC XY: 34253 AN XY: 134074

Gnomad AFR exome AF: 0.337

Gnomad AMR exome AF: 0.146

Gnomad ASJ exome AF: 0.182

Gnomad EAS exome AF: 0.122

Gnomad SAS exome AF: 0.329

Gnomad FIN exome AF: 0.244

Gnomad NFE exome AF: 0.272

Gnomad OTH exome AF: 0.250

GnomAD4 exome AF: 0.271 AC: 394410 AN: 1456196 Hom.: 55212 Cov.: 30 AF XY: 0.272 AC XY: 197385 AN XY: 724550

Gnomad4 AFR exome AF: 0.343

Gnomad4 AMR exome AF: 0.155

Gnomad4 ASJ exome AF: 0.186

Gnomad4 EAS exome AF: 0.149

Gnomad4 SAS exome AF: 0.334

Gnomad4 FIN exome AF: 0.243

Gnomad4 NFE exome AF: 0.276

Gnomad4 OTH exome AF: 0.265

GnomAD4 genome AF: 0.276 AC: 41924 AN: 151854 Hom.: 5986 Cov.: 21 AF XY: 0.271 AC XY: 20087 AN XY: 74198

Gnomad4 AFR AF: 0.338

Gnomad4 AMR AF: 0.200

Gnomad4 ASJ AF: 0.183

Gnomad4 EAS AF: 0.123

Gnomad4 SAS AF: 0.323

Gnomad4 FIN AF: 0.241

Gnomad4 NFE AF: 0.273

Gnomad4 OTH AF: 0.254

Alfa AF: 0.253 Hom.: 1030

Asia WGS AF: 0.225 AC: 783 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3833851; hg19: chr17-77753245;