11-66744819-GGGCGGCGGCGGCGGC-GGGCGGCGGCGGCGGCGGCGGCGGCGGC

Variant names:

• chr11-66744819-G-GGGCGGCGGCGGC
• rs567536854
• NM_001302084.2:c.-115_-104dupCGGCGGCGGCGG

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001302084.2(TOP6BL):​c.-115_-104dupCGGCGGCGGCGG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0074 (6 hom., cov: 0)
  • Exomes 𝑓: 0.0073 (76 hom.)
  • Failed GnomAD Quality Control
• 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 Likely_benign. Variant got -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOP6BL	NM_001302084.2	c.-115_-104dupCGGCGGCGGCGG		5_prime_UTR_variant	Exon 1 of 15	ENST00000540737.7	NP_001289013.1
TOP6BL	NM_024650.4	c.-56_-45dupCGGCGGCGGCGG		5_prime_UTR_variant	Exon 1 of 17		NP_078926.4
SPTBN2	XM_047427495.1	c.-495_-484dupGCCGCCGCCGCC		upstream_gene_variant			XP_047283451.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C11orf80	ENST00000540737	c.-115_-104dupCGGCGGCGGCGG		5_prime_UTR_variant	Exon 1 of 15	2	NM_001302084.2	ENSP00000444319.1

Frequencies

GnomAD3 genomes AF: 0.00740 AC: 1097 AN: 148172 Hom.: 6 Cov.: 0

Gnomad AFR AF: 0.00364

Gnomad AMI AF: 0.00224

Gnomad AMR AF: 0.00714

Gnomad ASJ AF: 0.00789

Gnomad EAS AF: 0.0102

Gnomad SAS AF: 0.00382

Gnomad FIN AF: 0.00966

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00945

Gnomad OTH AF: 0.0113

GnomAD3 exomes AF: 0.00153 AC: 23 AN: 15072 Hom.: 0 AF XY: 0.00153 AC XY: 14 AN XY: 9136

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000279

Gnomad FIN exome AF: 0.00278

Gnomad NFE exome AF: 0.00264

Gnomad OTH exome AF: 0.00250

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00730 AC: 7866 AN: 1078240 Hom.: 76 Cov.: 31 AF XY: 0.00727 AC XY: 3792 AN XY: 521640

Gnomad4 AFR exome AF: 0.00293

Gnomad4 AMR exome AF: 0.00511

Gnomad4 ASJ exome AF: 0.00597

Gnomad4 EAS exome AF: 0.00632

Gnomad4 SAS exome AF: 0.00261

Gnomad4 FIN exome AF: 0.0104

Gnomad4 NFE exome AF: 0.00765

Gnomad4 OTH exome AF: 0.00599

GnomAD4 genome AF: 0.00743 AC: 1102 AN: 148274 Hom.: 6 Cov.: 0 AF XY: 0.00707 AC XY: 511 AN XY: 72242

Gnomad4 AFR AF: 0.00370

Gnomad4 AMR AF: 0.00719

Gnomad4 ASJ AF: 0.00789

Gnomad4 EAS AF: 0.0102

Gnomad4 SAS AF: 0.00382

Gnomad4 FIN AF: 0.00966

Gnomad4 NFE AF: 0.00945

Gnomad4 OTH AF: 0.0117

Bravo AF: 0.00690

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;