rs12233351

Positions:

• chr22-19130379-T-C

Variant summary

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

The NM_022719.3(ESS2):​c.*3817A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0158 in 167,390 control chromosomes in the GnomAD database, including 126 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 0.015 (103 hom., cov: 33)
  • Exomes 𝑓: 0.020 (23 hom.)
• Consequence: ESS2 NM_022719.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESS2	NM_022719.3	c.*3817A>G		3_prime_UTR_variant	10/10	ENST00000252137.11	NP_073210.1
ESS2	XM_005261282.5	c.*3817A>G		3_prime_UTR_variant	10/10		XP_005261339.1
ESS2	XM_006724329.4	c.*3817A>G		3_prime_UTR_variant	10/10		XP_006724392.1
ESS2	NR_134304.2	n.5336A>G		non_coding_transcript_exon_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ESS2	ENST00000252137.11	c.*3817A>G		3_prime_UTR_variant	10/10	1	NM_022719.3	ENSP00000252137	P1

Frequencies

GnomAD3 genomes AF: 0.0153 AC: 2332 AN: 152200 Hom.: 101 Cov.: 33

Gnomad AFR AF: 0.00229

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0418

Gnomad ASJ AF: 0.00979

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.0242

Gnomad FIN AF: 0.0225

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00331

Gnomad OTH AF: 0.0162

GnomAD4 exome AF: 0.0200 AC: 302 AN: 15072 Hom.: 23 Cov.: 0 AF XY: 0.0194 AC XY: 172 AN XY: 8852

Gnomad4 AFR exome AF: 0.00360

Gnomad4 AMR exome AF: 0.0518

Gnomad4 ASJ exome AF: 0.0106

Gnomad4 EAS exome AF: 0.195

Gnomad4 SAS exome AF: 0.0201

Gnomad4 FIN exome AF: 0.0199

Gnomad4 NFE exome AF: 0.00481

Gnomad4 OTH exome AF: 0.00937

GnomAD4 genome AF: 0.0154 AC: 2343 AN: 152318 Hom.: 103 Cov.: 33 AF XY: 0.0180 AC XY: 1341 AN XY: 74482

Gnomad4 AFR AF: 0.00231

Gnomad4 AMR AF: 0.0424

Gnomad4 ASJ AF: 0.00979

Gnomad4 EAS AF: 0.182

Gnomad4 SAS AF: 0.0240

Gnomad4 FIN AF: 0.0225

Gnomad4 NFE AF: 0.00331

Gnomad4 OTH AF: 0.0170

Alfa AF: 0.0128 Hom.: 23

Bravo AF: 0.0178

Asia WGS AF: 0.0720 AC: 248 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.3
DANN	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs12233351; hg19: chr22-19117892;