chr2-219253950-C-CGGGGGGG

Variant names:

• chr2-219253950-C-CGGGGGGG
• NM_001355221.1:c.12+535_12+541dupGGGGGGG

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001355221.1(TUBA4B):​c.12+535_12+541dupGGGGGGG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000791 in 126,424 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000079 (0 hom., cov: 30)
• Consequence: TUBA4B NM_001355221.1 intron
• Clinical Significance: Not reported in ClinVar
• 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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUBA4B	NM_001355221.1	c.12+535_12+541dupGGGGGGG		intron_variant	Intron 1 of 3	ENST00000490341.3	NP_001342150.1
TUBA4A	NM_001278552.2	c.-43+138_-43+144dupCCCCCCC		intron_variant	Intron 1 of 3		NP_001265481.1
TUBA4A	XM_047445674.1	c.30+263_30+269dupCCCCCCC		intron_variant	Intron 1 of 3		XP_047301630.1
TUBA4A	NM_006000.3	c.-99_-93dupCCCCCCC		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+531_12+532insGGGGGGG		intron_variant	Intron 1 of 3	2	NM_001355221.1	ENSP00000487719.1
TUBA4A	ENST00000248437.9	c.-93_-92insCCCCCCC		upstream_gene_variant		1	NM_006000.3	ENSP00000248437.4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 126364 Hom.: 0 Cov.: 30 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 12

GnomAD4 genome AF: 0.00000791 AC: 1 AN: 126424 Hom.: 0 Cov.: 30 AF XY: 0.0000163 AC XY: 1 AN XY: 61470

Gnomad4 AFR AF: 0.0000276

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-220118672;