11-66744819-GGGCGGCGGCGGCGGC-GGGCGGC

Variant names:

• chr11-66744819-GGGCGGCGGC-G
• rs567536854
• NM_001302084.2:c.-112_-104delCGGCGGCGG

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001302084.2(TOP6BL):​c.-112_-104delCGGCGGCGG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000227 in 1,230,548 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00036 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00021 (0 hom.)
• Consequence: TOP6BL NM_001302084.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00

Genes affected

TOP6BL (HGNC:26197): (TOP6B like initiator of meiotic double strand breaks) Predicted to be involved in meiotic DNA double-strand break formation and reciprocal meiotic recombination. Predicted to be located in chromosome. Implicated in gestational trophoblastic neoplasm. [provided by Alliance of Genome Resources, Apr 2022]

SPTBN2 (HGNC:11276): (spectrin beta, non-erythrocytic 2) Spectrins are principle components of a cell's membrane-cytoskeleton and are composed of two alpha and two beta spectrin subunits. The protein encoded by this gene (SPTBN2), is called spectrin beta non-erythrocytic 2 or beta-III spectrin. It is related to, but distinct from, the beta-II spectrin gene which is also known as spectrin beta non-erythrocytic 1 (SPTBN1). SPTBN2 regulates the glutamate signaling pathway by stabilizing the glutamate transporter EAAT4 at the surface of the plasma membrane. Mutations in this gene cause a form of spinocerebellar ataxia, SCA5, that is characterized by neurodegeneration, progressive locomotor incoordination, dysarthria, and uncoordinated eye movements. [provided by RefSeq, Dec 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOP6BL	NM_001302084.2	c.-112_-104delCGGCGGCGG		5_prime_UTR_variant	Exon 1 of 15	ENST00000540737.7	NP_001289013.1
TOP6BL	NM_024650.4	c.-53_-45delCGGCGGCGG		5_prime_UTR_variant	Exon 1 of 17		NP_078926.4
SPTBN2	XM_047427495.1	c.-492_-484delGCCGCCGCC		upstream_gene_variant			XP_047283451.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C11orf80	ENST00000540737	c.-112_-104delCGGCGGCGG		5_prime_UTR_variant	Exon 1 of 15	2	NM_001302084.2	ENSP00000444319.1

Frequencies

GnomAD3 genomes AF: 0.000358 AC: 53 AN: 148174 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000516

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000267

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000407

Gnomad SAS AF: 0.000212

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000347

Gnomad OTH AF: 0.000981

GnomAD4 exome AF: 0.000208 AC: 225 AN: 1082272 Hom.: 0 AF XY: 0.000210 AC XY: 110 AN XY: 523444

Gnomad4 AFR exome AF: 0.000991

Gnomad4 AMR exome AF: 0.000511

Gnomad4 ASJ exome AF: 0.0000641

Gnomad4 EAS exome AF: 0.000342

Gnomad4 SAS exome AF: 0.0000952

Gnomad4 FIN exome AF: 0.0000394

Gnomad4 NFE exome AF: 0.000181

Gnomad4 OTH exome AF: 0.000364

GnomAD4 genome AF: 0.000364 AC: 54 AN: 148276 Hom.: 0 Cov.: 0 AF XY: 0.000374 AC XY: 27 AN XY: 72242

Gnomad4 AFR AF: 0.000515

Gnomad4 AMR AF: 0.000266

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000408

Gnomad4 SAS AF: 0.000212

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000347

Gnomad4 OTH AF: 0.00146

ClinVar

Not reported in ClinVar

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: rs567536854; hg19: chr11-66512290;