2-70229320-TAAAA-TAA

Position:

• chr2-70229320-TAAAA-TAA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_022173.4(TIA1):​c.223-4_223-3del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000241 in 1,078,752 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 0.0 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000024 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TIA1 NM_022173.4 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.341

Genes affected

TIA1 (HGNC:11802): (TIA1 cytotoxic granule associated RNA binding protein) The product encoded by this gene is a member of a RNA-binding protein family and possesses nucleolytic activity against cytotoxic lymphocyte (CTL) target cells. It has been suggested that this protein may be involved in the induction of apoptosis as it preferentially recognizes poly(A) homopolymers and induces DNA fragmentation in CTL targets. The major granule-associated species is a 15-kDa protein that is thought to be derived from the carboxyl terminus of the 40-kDa product by proteolytic processing. Alternative splicing resulting in different isoforms has been found for this gene. [provided by RefSeq, May 2017]

C2orf42 (HGNC:26056): (chromosome 2 open reading frame 42) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 26 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TIA1	NM_022173.4	c.223-4_223-3del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000433529.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TIA1	ENST00000433529.7	c.223-4_223-3del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		2	NM_022173.4	P4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 145258 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 AF: 0.0000241 AC: 26 AN: 1078752 Hom.: 0 AF XY: 0.0000205 AC XY: 11 AN XY: 536940

Gnomad4 AFR exome AF: 0.0000417

Gnomad4 AMR exome AF: 0.0000649

Gnomad4 ASJ exome AF: 0.0000533

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000646

Gnomad4 FIN exome AF: 0.0000762

Gnomad4 NFE exome AF: 0.0000145

Gnomad4 OTH exome AF: 0.0000454

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 145258 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 70522

Gnomad4 AFR AF: 0.00

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

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.25		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.25		Position offset: 15

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

Publications

LitVar

Other links and lift over

dbSNP: rs750862626; hg19: chr2-70456452;