rs7226408

Positions:

• chr18-36791898-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001271951.2(TPGS2):​c.658-4819G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 151,664 control chromosomes in the GnomAD database, including 3,691 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.20 (3691 hom., cov: 31)
• Consequence: TPGS2 NM_001271951.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.627

Genes affected

TPGS2 (HGNC:24561): (tubulin polyglutamylase complex subunit 2) This gene encodes a protein that is a component of the neuronal polyglutamylase complex, which plays a role in post-translational addition of glutamate residues to C-terminal tubulin tails. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPGS2	NM_001271951.2	c.658-4819G>A		intron_variant			NP_001258880.1
TPGS2	NM_001271953.2	c.658-4916G>A		intron_variant			NP_001258882.1
TPGS2	NM_001271955.2	c.383-4819G>A		intron_variant			NP_001258884.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPGS2	ENST00000587129.5	c.657+6551G>A		intron_variant		4		ENSP00000465551
TPGS2	ENST00000587382.5	c.621-1747G>A		intron_variant		3		ENSP00000467204
TPGS2	ENST00000590258.2	c.137+6551G>A		intron_variant		2		ENSP00000483592

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30564 AN: 151548 Hom.: 3690 Cov.: 31

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.00213

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.186

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.202 AC: 30616 AN: 151664 Hom.: 3691 Cov.: 31 AF XY: 0.200 AC XY: 14839 AN XY: 74116

Gnomad4 AFR AF: 0.331

Gnomad4 AMR AF: 0.198

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.00214

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.184

Alfa AF: 0.165 Hom.: 2170

Bravo AF: 0.209

Asia WGS AF: 0.0700 AC: 242 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.14

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7226408; hg19: chr18-34371861;