19-42249177-CG-TA

Variant names:

• chr19-42249177-CG-TA
• NM_006494.4:c.934_935delCGinsTA
• ERF p.Arg312*

Variant summary

Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PVS1

The NM_006494.4(ERF):​c.934_935delCGinsTA​(p.Arg312*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ERF NM_006494.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.14
• Publications: 0 publications found

Genes affected

ERF (HGNC:3444): (ETS2 repressor factor) ETS2 is a transcription factor and protooncogene involved in development, apoptosis, and the regulation of telomerase. The protein encoded by this gene binds to the ETS2 promoter and is a strong repressor of ETS2 transcription. Several transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Aug 2015]

ERF Gene-Disease associations (from GenCC):

• Chitayat syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• craniosynostosis 4

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, ClinGen, Ambry Genetics, G2P
• Crouzon syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• isolated scaphocephaly

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000268643 (HGNC:):

ACMG classification

Our verdict: Likely_pathogenic. The variant received 8 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006494.4. 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
	ERF	NM_006494.4	MANE Select	c.934_935delCGinsTA	p.Arg312*	stop_gained	N/A	NP_006485.2	P50548-1
	ERF	NM_001301035.2		c.709_710delCGinsTA	p.Arg237*	stop_gained	N/A	NP_001287964.1	P50548-2
	ERF	NM_001308402.2		c.709_710delCGinsTA	p.Arg237*	stop_gained	N/A	NP_001295331.1	P50548-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERF	ENST00000222329.9	TSL:1 MANE Select	c.934_935delCGinsTA	p.Arg312*	stop_gained	N/A	ENSP00000222329.3	P50548-1
	ENSG00000268643	ENST00000594664.1	TSL:3	c.22+5800_22+5801delCGinsTA		intron	N/A	ENSP00000470087.1	M0QYV0
	ERF	ENST00000440177.6	TSL:2	c.709_710delCGinsTA	p.Arg237*	stop_gained	N/A	ENSP00000388173.2	P50548-2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.1

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-42753329;