2-219253950-C-CG

Position:

• chr2-219253950-C-CG

Variant summary

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

The NM_001355221.1(TUBA4B):​c.12+541dupG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.029 in 503,686 control chromosomes in the GnomAD database, including 206 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.054 (205 hom., cov: 30)
  • Exomes 𝑓: 0.021 (1 hom.)
• Consequence: TUBA4B NM_001355221.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.431

Genes affected

TUBA4B (HGNC:18637): (tubulin alpha 4b) Predicted to enable GTP binding activity. Predicted to be a structural constituent of cytoskeleton. Predicted to be involved in microtubule cytoskeleton organization and mitotic cell cycle. Predicted to be active in cytoplasm and microtubule. [provided by Alliance of Genome Resources, Apr 2022]

TUBA4B (HGNC:):

TUBA4A (HGNC:12407): (tubulin alpha 4a) Microtubules of the eukaryotic cytoskeleton perform essential and diverse functions and are composed of a heterodimer of alpha and beta tubulin. The genes encoding these microtubule constituents are part of the tubulin superfamily, which is composed of six distinct families. Genes from the alpha, beta and gamma tubulin families are found in all eukaryotes. The alpha and beta tubulins represent the major components of microtubules, while gamma tubulin plays a critical role in the nucleation of microtubule assembly. There are multiple alpha and beta tubulin genes and they are highly conserved among and between species. This gene encodes an alpha tubulin that is a highly conserved homolog of a rat testis-specific alpha tubulin. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2013]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 2-219253950-C-CG is Benign according to our data. Variant chr2-219253950-C-CG is described in ClinVar as [Benign]. Clinvar id is 1235911.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0854 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUBA4B	NM_001355221.1	c.12+541dupG		intron_variant		ENST00000490341.3	NP_001342150.1
TUBA4A	NM_001278552.2	c.-43+144dupC		intron_variant			NP_001265481.1
TUBA4A	XM_047445674.1	c.30+269dupC		intron_variant			XP_047301630.1
TUBA4A	NM_006000.3	c.-93dupC		upstream_gene_variant		ENST00000248437.9	NP_005991.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUBA4B	ENST00000490341.3	c.12+541dupG		intron_variant		2	NM_001355221.1	ENSP00000487719.1
TUBA4A	ENST00000248437.9	c.-93dupC		upstream_gene_variant		1	NM_006000.3	ENSP00000248437.4

Frequencies

GnomAD3 genomes AF: 0.0538 AC: 6777 AN: 126068 Hom.: 205 Cov.: 30

Gnomad AFR AF: 0.0881

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.0332

Gnomad ASJ AF: 0.0235

Gnomad EAS AF: 0.00933

Gnomad SAS AF: 0.0216

Gnomad FIN AF: 0.0212

Gnomad MID AF: 0.0294

Gnomad NFE AF: 0.0467

Gnomad OTH AF: 0.0384

GnomAD4 exome AF: 0.0207 AC: 7817 AN: 377558 Hom.: 1 Cov.: 12 AF XY: 0.0212 AC XY: 3900 AN XY: 184024

Gnomad4 AFR exome AF: 0.0342

Gnomad4 AMR exome AF: 0.0308

Gnomad4 ASJ exome AF: 0.0228

Gnomad4 EAS exome AF: 0.00378

Gnomad4 SAS exome AF: 0.0181

Gnomad4 FIN exome AF: 0.0202

Gnomad4 NFE exome AF: 0.0209

Gnomad4 OTH exome AF: 0.0243

GnomAD4 genome AF: 0.0538 AC: 6781 AN: 126128 Hom.: 205 Cov.: 30 AF XY: 0.0519 AC XY: 3183 AN XY: 61324

Gnomad4 AFR AF: 0.0880

Gnomad4 AMR AF: 0.0331

Gnomad4 ASJ AF: 0.0235

Gnomad4 EAS AF: 0.00937

Gnomad4 SAS AF: 0.0217

Gnomad4 FIN AF: 0.0212

Gnomad4 NFE AF: 0.0467

Gnomad4 OTH AF: 0.0380

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

GeneDx

Aug 20, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs3051654; hg19: chr2-220118672;