NM_022719.3:c.-172T>A

Variant names:

• chr22-19144812-A-T
• rs737923
• NM_022719.3:c.-172T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54
• Publications: 14 publications found

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]

ACMG classification

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).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022719.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESS2	NM_022719.3	MANE Select	c.-172T>A		upstream_gene	N/A	NP_073210.1
	ESS2	NR_134304.2		n.-161T>A		upstream_gene	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESS2	ENST00000252137.11	TSL:1 MANE Select	c.-172T>A		upstream_gene	N/A	ENSP00000252137.6
	ESS2	ENST00000951416.1		c.-172T>A		upstream_gene	N/A	ENSP00000621475.1
	ESS2	ENST00000909110.1		c.-172T>A		upstream_gene	N/A	ENSP00000579169.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 924506 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 453178

African (AFR) AF: 0.00 AC: 0 AN: 18768

American (AMR) AF: 0.00 AC: 0 AN: 11754

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14962

East Asian (EAS) AF: 0.00 AC: 0 AN: 26466

South Asian (SAS) AF: 0.00 AC: 0 AN: 42332

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27736

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2782

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 740016

Other (OTH) AF: 0.00 AC: 0 AN: 39690

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.47
DANN	Benign	0.76
PhyloP100		-1.5
PromoterAI		-0.045	Neutral

Splicing

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

Other links and lift over

dbSNP: rs737923; hg19: chr22-19132325;