dbSNP rs80359865: ESCO2:c.1354-18G>A (chr8-27792650-G-A) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_ModeratePP5_Moderate

The NM_001017420.3(ESCO2):c.1354-18G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000823 in 1,457,964 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 pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

ESCO2
NM_001017420.3 intron

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1O:1

Conservation

PhyloP100: -0.155

Publications

1 publications found

Variant links:

Genes affected

ESCO2 (HGNC:27230): (establishment of sister chromatid cohesion N-acetyltransferase 2) This gene encodes a protein that may have acetyltransferase activity and may be required for the establishment of sister chromatid cohesion during the S phase of mitosis. Mutations in this gene have been associated with Roberts syndrome. [provided by RefSeq, Jul 2008]

ESCO2 Gene-Disease associations (from GenCC):

Roberts-SC phocomelia syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae)
Roberts syndrome
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics

ESCO2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

PP5

Variant 8-27792650-G-A is Pathogenic according to our data. Variant chr8-27792650-G-A is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 21236.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESCO2	NM_001017420.3 link	c.1354-18G>A		intron_variant	Intron 8 of 10	ENST00000305188.13	NP_001017420.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
ESCO2	ENST00000305188.13 link	c.1354-18G>A	intron_variant	Intron 8 of 10	1	NM_001017420.3	ENSP00000306999.8
ESCO2	ENST00000522378.5 link	n.*329-18G>A	intron_variant	Intron 6 of 11	1		ENSP00000428928.1
ESCO2	ENST00000397418.4 link	c.298-18G>A	intron_variant	Intron 3 of 6	5		ENSP00000380563.2
ESCO2	ENST00000518262.5 link	c.465+598G>A	intron_variant	Intron 5 of 5	3		ENSP00000428959.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000803

AC:

AN:

249050

AF XY:

0.00

show subpopulations

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:

0.0000929

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000823

AC:

AN:

1457964

Hom.:

Cov.:

AF XY:

0.00000689

AC XY:

AN XY:

725238

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33348

American (AMR)

AF:

0.00

AC:

AN:

44540

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26062

East Asian (EAS)

AF:

0.00

AC:

AN:

39514

South Asian (SAS)

AF:

0.00

AC:

AN:

85674

European-Finnish (FIN)

AF:

0.000206

AC:

AN:

53284

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4786

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1110650

Other (OTH)

AF:

0.00

AC:

AN:

60106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Roberts-SC phocomelia syndrome;C0796099:Juberg-Hayward syndrome

Pathogenic:1

Jan 08, 2024

Fulgent Genetics, Fulgent Genetics

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Roberts-SC phocomelia syndrome

Other:1

GeneReviews

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.0010

(source)

DANN

Benign

0.31

PhyloP100

-0.15

Mutation Taster

=33/67

disease causing (ClinVar)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.82

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.82

Position offset: 18

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over