Genetic Variant NM_181741.4:c.763-19_763-9dupTTTTTTTTTTT (chr2-147943530-G-GAAAAAAAAAAA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_181741.4(ORC4):c.763-19_763-9dupTTTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, 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.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ORC4
NM_181741.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.108

Publications

2 publications found

Variant links:

Genes affected

ORC4 (HGNC:8490): (origin recognition complex subunit 4) The origin recognition complex (ORC) is a highly conserved six subunit protein complex essential for the initiation of the DNA replication in eukaryotic cells. Studies in yeast demonstrated that ORC binds specifically to origins of replication and serves as a platform for the assembly of additional initiation factors such as Cdc6 and Mcm proteins. This gene encodes a subunit of the ORC complex. Several alternatively spliced transcript variants, some of which encode the same protein, have been reported for this gene. [provided by RefSeq, Oct 2010]

ORC4 Gene-Disease associations (from GenCC):

Meier-Gorlin syndrome 2
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, G2P
Meier-Gorlin syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ORC4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181741.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ORC4	NM_181741.4	MANE Select	c.763-19_763-9dupTTTTTTTTTTT	intron	N/A	NP_859525.1
ORC4	NM_001190879.3		c.763-19_763-9dupTTTTTTTTTTT	intron	N/A	NP_001177808.1
ORC4	NM_001374270.1		c.763-19_763-9dupTTTTTTTTTTT	intron	N/A	NP_001361199.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ORC4	ENST00000392857.10	TSL:1 MANE Select	c.763-9_763-8insTTTTTTTTTTT	intron	N/A	ENSP00000376597.5
ORC4	ENST00000264169.6	TSL:5	c.763-9_763-8insTTTTTTTTTTT	intron	N/A	ENSP00000264169.2
ORC4	ENST00000535373.5	TSL:5	c.763-9_763-8insTTTTTTTTTTT	intron	N/A	ENSP00000441953.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

131288

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000482

AC:

AN:

1037676

Hom.:

Cov.:

AF XY:

0.00000564

AC XY:

AN XY:

531678

show subpopulations

African (AFR)

AF:

0.0000416

AC:

AN:

24020

American (AMR)

AF:

0.0000262

AC:

AN:

38206

Ashkenazi Jewish (ASJ)

AF:

0.0000895

AC:

AN:

22350

East Asian (EAS)

AF:

0.00

AC:

AN:

36346

South Asian (SAS)

AF:

0.00

AC:

AN:

72324

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43908

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4382

European-Non Finnish (NFE)

AF:

0.00000133

AC:

AN:

750328

Other (OTH)

AF:

0.00

AC:

AN:

45812

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

131288

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

63336

African (AFR)

AF:

0.00

AC:

AN:

36884

American (AMR)

AF:

0.00

AC:

AN:

13234

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3088

East Asian (EAS)

AF:

0.00

AC:

AN:

4568

South Asian (SAS)

AF:

0.00

AC:

AN:

4002

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7314

Middle Eastern (MID)

AF:

0.00

AC:

AN:

266

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

59322

Other (OTH)

AF:

0.00

AC:

AN:

1832

Alfa

AF:

0.00

Hom.:

288

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.11

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over