rs193920793

Variant names:

• chr17-55268070-G-GA
• rs193920793
• NM_002126.5:c.436dupA

Variant summary

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

The NM_002126.5(HLF):​c.436dupA​(p.Ser146LysfsTer20) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HLF NM_002126.5 frameshift
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 5.88
• Publications: 0 publications found

Genes affected

HLF (HGNC:4977): (HLF transcription factor, PAR bZIP family member) This gene encodes a member of the proline and acidic-rich (PAR) protein family, a subset of the bZIP transcription factors. The encoded protein forms homodimers or heterodimers with other PAR family members and binds sequence-specific promoter elements to activate transcription. Chromosomal translocations fusing portions of this gene with the E2A gene cause a subset of childhood B-lineage acute lymphoid leukemias. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

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_002126.5. 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
	HLF	NM_002126.5	MANE Select	c.436dupA	p.Ser146LysfsTer20	frameshift	Exon 2 of 4	NP_002117.1
	HLF	NM_001330375.2		c.181dupA	p.Ser61LysfsTer20	frameshift	Exon 2 of 4	NP_001317304.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLF	ENST00000226067.10	TSL:1 MANE Select	c.436dupA	p.Ser146LysfsTer20	frameshift	Exon 2 of 4	ENSP00000226067.5
	HLF	ENST00000572002.1	TSL:3	c.256dupA	p.Ser86LysfsTer20	frameshift	Exon 1 of 3	ENSP00000461455.1
	HLF	ENST00000430986.6	TSL:2	c.181dupA	p.Ser61LysfsTer20	frameshift	Exon 2 of 4	ENSP00000402496.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Prostate cancer (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.9

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: rs193920793; hg19: chr17-53345431;