9-137049054-GC-G

Variant names:

• chr9-137049054-GC-G
• NM_203468.3:c.1170delG

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP5_Moderate

The NM_203468.3(ENTPD2):​c.1170delG​(p.Gln391AsnfsTer19) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ENTPD2 NM_203468.3 frameshift
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: -0.246
• Publications: 0 publications found

Genes affected

ENTPD2 (HGNC:3364): (ectonucleoside triphosphate diphosphohydrolase 2) The protein encoded by this gene is the type 2 enzyme of the ecto-nucleoside triphosphate diphosphohydrolase family (E-NTPDase). E-NTPDases are a family of ecto-nucleosidases that hydrolyze 5'-triphosphates. This ecto-ATPase is an integral membrane protein. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 9-137049054-GC-G is Pathogenic according to our data. Variant chr9-137049054-GC-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3256927.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENTPD2	NM_203468.3	c.1170delG	p.Gln391AsnfsTer19	frameshift_variant	Exon 8 of 9	ENST00000355097.7	NP_982293.1
ENTPD2	XM_011519212.3	c.861delG	p.Gln288AsnfsTer19	frameshift_variant	Exon 7 of 8		XP_011517514.1
ENTPD2	NM_001246.4	c.1150-49delG		intron_variant	Intron 7 of 8		NP_001237.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENTPD2	ENST00000355097.7	c.1170delG	p.Gln391AsnfsTer19	frameshift_variant	Exon 8 of 9	1	NM_203468.3	ENSP00000347213.2
ENTPD2	ENST00000460614.1	n.559delG		non_coding_transcript_exon_variant	Exon 1 of 2	1
ENTPD2	ENST00000312665.7	c.1150-49delG		intron_variant	Intron 7 of 8	1		ENSP00000312494.5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1381678 Hom.: 0 Cov.: 68 AF XY: 0.00 AC XY: 0 AN XY: 681600

African (AFR) AF: 0.00 AC: 0 AN: 31272

American (AMR) AF: 0.00 AC: 0 AN: 35280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25032

East Asian (EAS) AF: 0.00 AC: 0 AN: 35516

South Asian (SAS) AF: 0.00 AC: 0 AN: 79110

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5582

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1076830

Other (OTH) AF: 0.00 AC: 0 AN: 57636

GnomAD4 genome Cov.: 34

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Susceptibility to severe COVID-19 Pathogenic:1

Jul 22, 2024

Molecular Medicine Center, Medical University of Sofia

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: research

Novel (unreported in gnomAD or dbSNP until April 2024) variant found in severely infected COVID-19 Bulgarian patients in a research study. Variant is classified as likely pathogenic according to the ACMG criteria: PM2,PVS1. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

hg19: chr9-139943506;