2-219250304-C-T

Variant names:

• chr2-219250304-C-T
• rs11556349
• NM_006000.3:c.*48G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006000.3(TUBA4A):​c.*48G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0109 in 1,552,174 control chromosomes in the GnomAD database, including 382 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (52 hom., cov: 32)
  • Exomes 𝑓: 0.011 (330 hom.)
• Consequence: TUBA4A NM_006000.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.930
• Publications: 4 publications found

Genes affected

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]

STK16 (HGNC:11394): (serine/threonine kinase 16) Predicted to enable protein serine/threonine kinase activity. Involved in protein autophosphorylation. Located in cytosol; nucleoplasm; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 2-219250304-C-T is Benign according to our data. Variant chr2-219250304-C-T is described in ClinVar as Benign. ClinVar VariationId is 1227287.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0629 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006000.3. 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
	TUBA4A	NM_006000.3	MANE Select	c.*48G>A		3_prime_UTR	Exon 4 of 4	NP_005991.1	P68366-1
	STK16	NM_001330213.2	MANE Select	c.*1745C>T		3_prime_UTR	Exon 8 of 8	NP_001317142.1	O75716
	TUBA4A	NM_001278552.2		c.*48G>A		3_prime_UTR	Exon 4 of 4	NP_001265481.1	P68366-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBA4A	ENST00000248437.9	TSL:1 MANE Select	c.*48G>A		3_prime_UTR	Exon 4 of 4	ENSP00000248437.4	P68366-1
	STK16	ENST00000396738.7	TSL:2 MANE Select	c.*1745C>T		3_prime_UTR	Exon 8 of 8	ENSP00000379964.2	O75716
	STK16	ENST00000409638.7	TSL:1	c.*1745C>T		3_prime_UTR	Exon 8 of 8	ENSP00000386928.3	O75716

Frequencies

GnomAD3 genomes AF: 0.0128 AC: 1942 AN: 152224 Hom.: 47 Cov.: 32

Gnomad AFR AF: 0.00364

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0655

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.00497

Gnomad FIN AF: 0.00631

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00963

Gnomad OTH AF: 0.0148

GnomAD2 exomes AF: 0.0209 AC: 4306 AN: 205982 AF XY: 0.0173

Gnomad AFR exome AF: 0.00274

Gnomad AMR exome AF: 0.115

Gnomad ASJ exome AF: 0.00144

Gnomad EAS exome AF: 0.000528

Gnomad FIN exome AF: 0.00752

Gnomad NFE exome AF: 0.00926

Gnomad OTH exome AF: 0.0174

GnomAD4 exome AF: 0.0107 AC: 15042 AN: 1399832 Hom.: 330 Cov.: 31 AF XY: 0.0102 AC XY: 7059 AN XY: 689624

African (AFR) AF: 0.00226 AC: 71 AN: 31418

American (AMR) AF: 0.105 AC: 3737 AN: 35624

Ashkenazi Jewish (ASJ) AF: 0.00137 AC: 30 AN: 21928

East Asian (EAS) AF: 0.000435 AC: 17 AN: 39068

South Asian (SAS) AF: 0.00518 AC: 398 AN: 76878

European-Finnish (FIN) AF: 0.00729 AC: 373 AN: 51134

Middle Eastern (MID) AF: 0.00330 AC: 18 AN: 5454

European-Non Finnish (NFE) AF: 0.00905 AC: 9775 AN: 1080652

Other (OTH) AF: 0.0108 AC: 623 AN: 57676

GnomAD4 genome AF: 0.0128 AC: 1953 AN: 152342 Hom.: 52 Cov.: 32 AF XY: 0.0129 AC XY: 958 AN XY: 74488

African (AFR) AF: 0.00363 AC: 151 AN: 41588

American (AMR) AF: 0.0662 AC: 1014 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3470

East Asian (EAS) AF: 0.000964 AC: 5 AN: 5188

South Asian (SAS) AF: 0.00518 AC: 25 AN: 4826

European-Finnish (FIN) AF: 0.00631 AC: 67 AN: 10612

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00961 AC: 654 AN: 68030

Other (OTH) AF: 0.0142 AC: 30 AN: 2114

Alfa AF: 0.0133 Hom.: 58

Bravo AF: 0.0182

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	12
DANN	Benign	0.80
PhyloP100		-0.93
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: rs11556349; hg19: chr2-220115026;