chr17-2042612-C-T

Variant names:

• chr17-2042612-C-T
• rs773578601
• NM_080822.3:c.192C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_080822.3(OVCA2):​c.192C>T​(p.Cys64Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000219 in 1,367,142 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: OVCA2 NM_080822.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.899
• Publications: 0 publications found

Genes affected

OVCA2 (HGNC:24203): (OVCA2 serine hydrolase domain containing) Involved in response to retinoic acid. Located in cytoplasm. Biomarker of ovarian cancer. [provided by Alliance of Genome Resources, Apr 2022]

DPH1 (HGNC:3003): (diphthamide biosynthesis 1) The protein encoded by this gene is an enzyme involved in the biosynthesis of diphthamide, a modified histidine found only in elongation factor-2 (EEF2). Diphthamide residues in EEF2 are targeted for ADP-ribosylation by diphtheria toxin and Pseudomonas exotoxin A. Defects in this gene have been associated with both ovarian cancer and autosomal recessive intellectual disability with short stature, craniofacial, and ectodermal anomalies. [provided by RefSeq, Oct 2016]

DPH1 Gene-Disease associations (from GenCC):

• developmental delay with short stature, dysmorphic facial features, and sparse hair

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• craniofacial dysplasia-short stature-ectodermal anomalies-intellectual disability syndrome

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, PanelApp Australia, Orphanet
• developmental delay with short stature, dysmorphic facial features, and sparse hair 1

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 17-2042612-C-T is Benign according to our data. Variant chr17-2042612-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3389565.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.899 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080822.3. 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
	OVCA2	NM_080822.3	MANE Select	c.192C>T	p.Cys64Cys	synonymous	Exon 2 of 2	NP_543012.1	Q8WZ82
	DPH1	NM_001383.6	MANE Select	c.*26C>T		3_prime_UTR	Exon 13 of 13	NP_001374.4	Q9BZG8-4
	DPH1	NM_001346574.1		c.*26C>T		3_prime_UTR	Exon 13 of 13	NP_001333503.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OVCA2	ENST00000572195.3	TSL:1 MANE Select	c.192C>T	p.Cys64Cys	synonymous	Exon 2 of 2	ENSP00000461388.1	Q8WZ82
	DPH1	ENST00000263083.12	TSL:1 MANE Select	c.*26C>T		3_prime_UTR	Exon 13 of 13	ENSP00000263083.7	Q9BZG8-4
	DPH1	ENST00000571710.6	TSL:1	c.*755C>T		3_prime_UTR	Exon 5 of 5	ENSP00000460813.1	I3L3X9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000575 AC: 1 AN: 173918 AF XY: 0.0000109

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000120

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000219 AC: 3 AN: 1367142 Hom.: 0 Cov.: 32 AF XY: 0.00000149 AC XY: 1 AN XY: 670104

African (AFR) AF: 0.00 AC: 0 AN: 30218

American (AMR) AF: 0.00 AC: 0 AN: 28778

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19864

East Asian (EAS) AF: 0.00 AC: 0 AN: 38948

South Asian (SAS) AF: 0.00 AC: 0 AN: 69452

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49502

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5304

European-Non Finnish (NFE) AF: 0.00000281 AC: 3 AN: 1068818

Other (OTH) AF: 0.00 AC: 0 AN: 56258

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	9.1
DANN	Benign	0.89
PhyloP100		0.90
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs773578601; hg19: chr17-1945906;