Genetic Variant ESS2:c.-172T>A (chr22-19144812-A-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_022719.3(ESS2):c.-172T>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ESS2
NM_022719.3 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.54

Publications

14 publications found

Variant links:

Genes affected

ESS2 (HGNC:16817): (ess-2 splicing factor homolog) This gene is located within the minimal DGS critical region (MDGCR) thought to contain the gene(s) responsible for a group of developmental disorders. These disorders include DiGeorge syndrome, velocardiofacial syndrome, conotruncal anomaly face syndrome, and some familial or sporadic conotruncal cardiac defects which have been associated with microdeletion of 22q11.2. The encoded protein may be a component of C complex spliceosomes, and the orthologous protein in the mouse localizes to the nucleus. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2015]

ESS2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESS2	NM_022719.3 link	c.-172T>A		upstream_gene_variant		ENST00000252137.11	NP_073210.1	Q96DF8

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
ESS2	ENST00000252137.11 link	c.-172T>A	upstream_gene_variant	1	NM_022719.3	ENSP00000252137.6	Q96DF8
ESS2	ENST00000434568.5 link	n.-172T>A	upstream_gene_variant	5		ENSP00000388524.1	F8WEF8
ESS2	ENST00000469466.1 link	n.-153T>A	upstream_gene_variant	3
ESS2	ENST00000472073.1 link	n.-179T>A	upstream_gene_variant	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

924506

Hom.:

AF XY:

0.00

AC XY:

AN XY:

453178

African (AFR)

AF:

0.00

AC:

AN:

18768

American (AMR)

AF:

0.00

AC:

AN:

11754

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14962

East Asian (EAS)

AF:

0.00

AC:

AN:

26466

South Asian (SAS)

AF:

0.00

AC:

AN:

42332

European-Finnish (FIN)

AF:

0.00

AC:

AN:

27736

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2782

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

740016

Other (OTH)

AF:

0.00

AC:

AN:

39690

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.47

(source)

DANN

Benign

0.76

PhyloP100

-1.5

PromoterAI

-0.045

Neutral

(source)

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over