rs737923

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr22-19144812-A-G
• chr22-19144812-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022719.3(ESS2):​c.-172T>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 1,073,982 control chromosomes in the GnomAD database, including 81,214 homozygotes. 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: 𝑓 0.41 (13432 hom., cov: 32)
  • Exomes 𝑓: 0.37 (67782 hom.)
• Consequence: ESS2 NM_022719.3 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ESS2	ENST00000252137.11	c.-172T>C		upstream_gene_variant		1	NM_022719.3	ENSP00000252137.6
ESS2	ENST00000434568.5	n.-172T>C		upstream_gene_variant		5		ENSP00000388524.1
ESS2	ENST00000469466.1	n.-153T>C		upstream_gene_variant		3
ESS2	ENST00000472073.1	n.-179T>C		upstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62734 AN: 151970 Hom.: 13390 Cov.: 32

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.690

Gnomad SAS AF: 0.491

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.404

GnomAD4 exome AF: 0.375 AC: 345385 AN: 921894 Hom.: 67782 AF XY: 0.377 AC XY: 170305 AN XY: 451982

Gnomad4 AFR exome AF: 0.464

Gnomad4 AMR exome AF: 0.393

Gnomad4 ASJ exome AF: 0.379

Gnomad4 EAS exome AF: 0.736

Gnomad4 SAS exome AF: 0.459

Gnomad4 FIN exome AF: 0.390

Gnomad4 NFE exome AF: 0.353

Gnomad4 OTH exome AF: 0.390

GnomAD4 genome AF: 0.413 AC: 62838 AN: 152088 Hom.: 13432 Cov.: 32 AF XY: 0.419 AC XY: 31123 AN XY: 74340

Gnomad4 AFR AF: 0.461

Gnomad4 AMR AF: 0.417

Gnomad4 ASJ AF: 0.380

Gnomad4 EAS AF: 0.690

Gnomad4 SAS AF: 0.491

Gnomad4 FIN AF: 0.404

Gnomad4 NFE AF: 0.363

Gnomad4 OTH AF: 0.411

Alfa AF: 0.371 Hom.: 11118

Bravo AF: 0.412

Asia WGS AF: 0.596 AC: 2071 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.56
DANN	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs737923; hg19: chr22-19132325;