rs587778704

Variant names:

• chr4-105234900-GAAC-G
• rs587778704
• NM_001127208.3:c.962_964delAAC

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PM4_Supporting

The NM_001127208.3(TET2):​c.962_964delAAC​(p.Gln321del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.0000041 in 1,461,784 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: TET2 NM_001127208.3 disruptive_inframe_deletion
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 4.51
• Publications: 1 publications found

Genes affected

TET2 (HGNC:25941): (tet methylcytosine dioxygenase 2) The protein encoded by this gene is a methylcytosine dioxygenase that catalyzes the conversion of methylcytosine to 5-hydroxymethylcytosine. The encoded protein is involved in myelopoiesis, and defects in this gene have been associated with several myeloproliferative disorders. Two variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2011]

TET2-AS1 (HGNC:41125): (TET2 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_001127208.3. Strenght limited to Supporting due to length of the change: 1aa.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001127208.3. 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
	TET2	NM_001127208.3	MANE Select	c.962_964delAAC	p.Gln321del	disruptive_inframe_deletion	Exon 3 of 11	NP_001120680.1
	TET2	NM_017628.4		c.962_964delAAC	p.Gln321del	disruptive_inframe_deletion	Exon 3 of 3	NP_060098.3
	TET2-AS1	NR_126420.1		n.319-57231_319-57229delGTT		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TET2	ENST00000380013.9	TSL:5 MANE Select	c.962_964delAAC	p.Gln321del	disruptive_inframe_deletion	Exon 3 of 11	ENSP00000369351.4
	TET2	ENST00000513237.5	TSL:1	c.1025_1027delAAC	p.Gln342del	disruptive_inframe_deletion	Exon 3 of 11	ENSP00000425443.1
	TET2	ENST00000540549.5	TSL:1	c.962_964delAAC	p.Gln321del	disruptive_inframe_deletion	Exon 3 of 11	ENSP00000442788.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000120 AC: 3 AN: 250178 AF XY: 0.00000739

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000164

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461784 Hom.: 0 AF XY: 0.00000275 AC XY: 2 AN XY: 727188

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39662

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111984

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions as Germline

Significance: not provided

Revision: no classification provided

Pathogenic	VUS	Benign	Condition
-	-	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.5

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: rs587778704; hg19: chr4-106156057;