6-3224590-GAA-GAAA

Variant names:

• chr6-3224590-G-GA
• rs10717744
• NM_178012.5:c.*160dupT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_178012.5(TUBB2B):​c.*160dupT variant causes a 3 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: not found (cov: 0)
  • Exomes 𝑓: 0.0000099 (0 hom.)
• Consequence: TUBB2B NM_178012.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.235
• Publications: 0 publications found

Genes affected

TUBB2B (HGNC:30829): (tubulin beta 2B class IIb) The protein encoded by this gene is a beta isoform of tubulin, which binds GTP and is a major component of microtubules. This gene is highly similar to TUBB2A and TUBB2C. Defects in this gene are a cause of asymmetric polymicrogyria. [provided by RefSeq, Mar 2010]

TUBB2B Gene-Disease associations (from GenCC):

• complex cortical dysplasia with other brain malformations

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• complex cortical dysplasia with other brain malformations 7

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P
• congenital fibrosis of extraocular muscles

  Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Genomics England PanelApp
• tubulinopathy-associated dysgyria

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• cerebellar ataxia, intellectual disability, and dysequilibrium

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178012.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBB2B	NM_178012.5	MANE Select	c.*160dupT		3_prime_UTR	Exon 4 of 4	NP_821080.1	A0A384MEE3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBB2B	ENST00000259818.8	TSL:1 MANE Select	c.*160dupT		3_prime_UTR	Exon 4 of 4	ENSP00000259818.6	Q9BVA1
	TUBB2B	ENST00000473006.1	TSL:3	n.1615dupT		non_coding_transcript_exon	Exon 4 of 4
	TUBB2B	ENST00000680070.1		n.2428dupT		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000988 AC: 9 AN: 910718 Hom.: 0 Cov.: 0 AF XY: 0.0000154 AC XY: 7 AN XY: 453688

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 21012

American (AMR) AF: 0.00 AC: 0 AN: 19732

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16638

East Asian (EAS) AF: 0.00 AC: 0 AN: 33142

South Asian (SAS) AF: 0.00 AC: 0 AN: 55488

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34952

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2948

European-Non Finnish (NFE) AF: 0.0000131 AC: 9 AN: 685922

Other (OTH) AF: 0.00 AC: 0 AN: 40884

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000183422), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.23

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: rs10717744; hg19: chr6-3224824;