11-111358698-T-TCTCA

Variant names:

• chr11-111358698-T-TCTCA
• rs1555074608
• NM_006235.3:c.147+89_147+90insTGAG

Variant summary

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

The NM_006235.3(POU2AF1):​c.147+89_147+90insTGAG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000476 in 1,450,760 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000075 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000044 (1 hom.)
• Consequence: POU2AF1 NM_006235.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.40
• Publications: 0 publications found

Genes affected

POU2AF1 (HGNC:9211): (POU class 2 homeobox associating factor 1) Enables transcription coactivator activity. Involved in positive regulation of transcription by RNA polymerase II. Part of RNA polymerase II transcription regulator complex. [provided by Alliance of Genome Resources, Apr 2022]

POU2AF1 Gene-Disease associations (from GenCC):

• agammaglobulinemia

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

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_006235.3. 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
	POU2AF1	NM_006235.3	MANE Select	c.147+89_147+90insTGAG		intron	N/A	NP_006226.2	Q16633

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU2AF1	ENST00000393067.8	TSL:1 MANE Select	c.147+89_147+90insTGAG		intron	N/A	ENSP00000376786.3	Q16633
	POU2AF1	ENST00000531398.1	TSL:4	c.153+89_153+90insTGAG		intron	N/A	ENSP00000433527.1	E9PKH4
	POU2AF1	ENST00000525584.1	TSL:3	n.266+89_266+90insTGAG		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000749 AC: 11 AN: 146958 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000135

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000204

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000121

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000445 AC: 58 AN: 1303678 Hom.: 1 AF XY: 0.0000448 AC XY: 29 AN XY: 646788

African (AFR) AF: 0.0000336 AC: 1 AN: 29766

American (AMR) AF: 0.00 AC: 0 AN: 35386

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24494

East Asian (EAS) AF: 0.00 AC: 0 AN: 34578

South Asian (SAS) AF: 0.0000392 AC: 3 AN: 76510

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34802

Middle Eastern (MID) AF: 0.000224 AC: 1 AN: 4464

European-Non Finnish (NFE) AF: 0.0000496 AC: 50 AN: 1008602

Other (OTH) AF: 0.0000545 AC: 3 AN: 55076

GnomAD4 genome AF: 0.0000748 AC: 11 AN: 147082 Hom.: 0 Cov.: 34 AF XY: 0.0000417 AC XY: 3 AN XY: 71860

African (AFR) AF: 0.00 AC: 0 AN: 39734

American (AMR) AF: 0.000135 AC: 2 AN: 14868

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3384

East Asian (EAS) AF: 0.000205 AC: 1 AN: 4882

South Asian (SAS) AF: 0.00 AC: 0 AN: 4566

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10114

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 272

European-Non Finnish (NFE) AF: 0.000121 AC: 8 AN: 66324

Other (OTH) AF: 0.00 AC: 0 AN: 2040

Alfa AF: 0.0000843 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs1555074608; hg19: chr11-111229423;