rs750862626

Variant names:

• chr2-70229320-TAAAAA-T
• rs750862626
• NM_022173.4:c.223-7_223-3delTTTTT

Your query was ambiguous. Multiple possible variants found:

• chr2-70229320-TAAAAA-T
• chr2-70229320-TAAAAA-TA
• chr2-70229320-TAAAAA-TAA
• chr2-70229320-TAAAAA-TAAA
• chr2-70229320-TAAAAA-TAAAA
• chr2-70229320-TAAAAA-TAAAAAA
• chr2-70229320-TAAAAA-TAAAAAAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_022173.4(TIA1):​c.223-7_223-3delTTTTT variant causes a splice region, intron change. The variant allele was found at a frequency of 0.000000925 in 1,080,598 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: not found (cov: 30)
  • Exomes 𝑓: 9.3e-7 (0 hom.)
• Consequence: TIA1 NM_022173.4 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.28
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022173.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIA1	NM_022173.4	MANE Select	c.223-7_223-3delTTTTT		splice_region intron	N/A	NP_071505.2
	TIA1	NM_001351508.2		c.223-7_223-3delTTTTT		splice_region intron	N/A	NP_001338437.1
	TIA1	NM_001351509.2		c.229-7_229-3delTTTTT		splice_region intron	N/A	NP_001338438.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIA1	ENST00000433529.7	TSL:2 MANE Select	c.223-7_223-3delTTTTT		splice_region intron	N/A	ENSP00000401371.2
	TIA1	ENST00000415783.6	TSL:1	c.223-7_223-3delTTTTT		splice_region intron	N/A	ENSP00000404023.2
	TIA1	ENST00000416149.6	TSL:1	c.223-7_223-3delTTTTT		splice_region intron	N/A	ENSP00000413751.2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 9.25e-7 AC: 1 AN: 1080598 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 537774

African (AFR) AF: 0.00 AC: 0 AN: 24018

American (AMR) AF: 0.00 AC: 0 AN: 30866

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18798

East Asian (EAS) AF: 0.00 AC: 0 AN: 29690

South Asian (SAS) AF: 0.00 AC: 0 AN: 62028

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39424

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4224

European-Non Finnish (NFE) AF: 0.00000121 AC: 1 AN: 827460

Other (OTH) AF: 0.00 AC: 0 AN: 44090

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.3

Splicing

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

Other links and lift over

dbSNP: rs750862626; hg19: chr2-70456452;