chr6-3224590-GA-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_178012.5(TUBB2B):​c.*160delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.94 (66879 hom., cov: 0)
  • Exomes 𝑓: 0.94 (399385 hom.)
• Consequence: TUBB2B NM_178012.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.235
• Publications: 1 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 6-3224590-GA-G is Benign according to our data. Variant chr6-3224590-GA-G is described in ClinVar as Benign. ClinVar VariationId is 1261368.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

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.*160delT		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.*160delT		3_prime_UTR	Exon 4 of 4	ENSP00000259818.6	Q9BVA1
	TUBB2B	ENST00000473006.1	TSL:3	n.1615delT		non_coding_transcript_exon	Exon 4 of 4
	TUBB2B	ENST00000680070.1		n.2428delT		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.936 AC: 142285 AN: 151978 Hom.: 66829 Cov.: 0

Gnomad AFR AF: 0.959

Gnomad AMI AF: 0.946

Gnomad AMR AF: 0.879

Gnomad ASJ AF: 0.878

Gnomad EAS AF: 0.748

Gnomad SAS AF: 0.876

Gnomad FIN AF: 0.974

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.951

Gnomad OTH AF: 0.917

GnomAD4 exome AF: 0.935 AC: 851594 AN: 910380 Hom.: 399385 Cov.: 0 AF XY: 0.934 AC XY: 423418 AN XY: 453546

African (AFR) AF: 0.961 AC: 20182 AN: 21006

American (AMR) AF: 0.862 AC: 17009 AN: 19730

Ashkenazi Jewish (ASJ) AF: 0.875 AC: 14561 AN: 16636

East Asian (EAS) AF: 0.764 AC: 25308 AN: 33136

South Asian (SAS) AF: 0.877 AC: 48629 AN: 55476

European-Finnish (FIN) AF: 0.972 AC: 33970 AN: 34950

Middle Eastern (MID) AF: 0.896 AC: 2638 AN: 2944

European-Non Finnish (NFE) AF: 0.950 AC: 651457 AN: 685640

Other (OTH) AF: 0.926 AC: 37840 AN: 40862

GnomAD4 genome AF: 0.936 AC: 142394 AN: 152096 Hom.: 66879 Cov.: 0 AF XY: 0.934 AC XY: 69464 AN XY: 74346

African (AFR) AF: 0.959 AC: 39781 AN: 41474

American (AMR) AF: 0.879 AC: 13419 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.878 AC: 3046 AN: 3468

East Asian (EAS) AF: 0.748 AC: 3862 AN: 5164

South Asian (SAS) AF: 0.876 AC: 4217 AN: 4812

European-Finnish (FIN) AF: 0.974 AC: 10327 AN: 10598

Middle Eastern (MID) AF: 0.915 AC: 269 AN: 294

European-Non Finnish (NFE) AF: 0.951 AC: 64681 AN: 68000

Other (OTH) AF: 0.916 AC: 1929 AN: 2106

Alfa AF: 0.952 Hom.: 3073

Bravo AF: 0.928

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.23
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV52533043;