2-219253950-CGGGGGG-CGGGGG

Variant names:

• chr2-219253950-CG-C
• rs3051654
• NM_001355221.1:c.12+541delG

Variant summary

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

The NM_001355221.1(TUBA4B):​c.12+541delG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0969 in 464,262 control chromosomes in the GnomAD database, including 1,644 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.087 (940 hom., cov: 30)
  • Exomes 𝑓: 0.10 (704 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]

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-CG-C is Benign according to our data. Variant chr2-219253950-CG-C is described in ClinVar as [Benign]. Clinvar id is 1241194.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUBA4B	NM_001355221.1	c.12+541delG		intron_variant	Intron 1 of 3	ENST00000490341.3	NP_001342150.1
TUBA4A	NM_001278552.2	c.-43+144delC		intron_variant	Intron 1 of 3		NP_001265481.1
TUBA4A	XM_047445674.1	c.30+269delC		intron_variant	Intron 1 of 3		XP_047301630.1
TUBA4A	NM_006000.3	c.-93delC		upstream_gene_variant		ENST00000248437.9	NP_005991.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUBA4B	ENST00000490341.3	c.12+532delG		intron_variant	Intron 1 of 3	2	NM_001355221.1	ENSP00000487719.1
TUBA4A	ENST00000248437.9	c.-93delC		upstream_gene_variant		1	NM_006000.3	ENSP00000248437.4

Frequencies

GnomAD3 genomes AF: 0.0870 AC: 10982 AN: 126276 Hom.: 937 Cov.: 30

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.0107

Gnomad AMR AF: 0.0337

Gnomad ASJ AF: 0.0258

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.0262

Gnomad FIN AF: 0.0334

Gnomad MID AF: 0.0420

Gnomad NFE AF: 0.0178

Gnomad OTH AF: 0.0771

GnomAD4 exome AF: 0.101 AC: 33980 AN: 337928 Hom.: 704 Cov.: 12 AF XY: 0.0971 AC XY: 15992 AN XY: 164638

Gnomad4 AFR exome AF: 0.357

Gnomad4 AMR exome AF: 0.0838

Gnomad4 ASJ exome AF: 0.0728

Gnomad4 EAS exome AF: 0.189

Gnomad4 SAS exome AF: 0.123

Gnomad4 FIN exome AF: 0.0638

Gnomad4 NFE exome AF: 0.0864

Gnomad4 OTH exome AF: 0.111

GnomAD4 genome AF: 0.0871 AC: 11010 AN: 126334 Hom.: 940 Cov.: 30 AF XY: 0.0861 AC XY: 5289 AN XY: 61412

Gnomad4 AFR AF: 0.233

Gnomad4 AMR AF: 0.0337

Gnomad4 ASJ AF: 0.0258

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.0260

Gnomad4 FIN AF: 0.0334

Gnomad4 NFE AF: 0.0179

Gnomad4 OTH AF: 0.0775

Bravo AF: 0.0824

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 17, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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;