22-19130379-T-C

Variant names:

• chr22-19130379-T-C
• rs12233351
• NM_022719.3:c.*3817A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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]

ENSG00000223461 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

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.*3817A>G		3_prime_UTR	Exon 10 of 10	NP_073210.1
	ESS2	NR_134304.2		n.5336A>G		non_coding_transcript_exon	Exon 10 of 10

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESS2	ENST00000252137.11	TSL:1 MANE Select	c.*3817A>G		3_prime_UTR	Exon 10 of 10	ENSP00000252137.6
	ENSG00000223461	ENST00000752497.1		n.146-4400T>C		intron	N/A

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

African (AFR) AF: 0.00360 AC: 1 AN: 278

American (AMR) AF: 0.0518 AC: 17 AN: 328

Ashkenazi Jewish (ASJ) AF: 0.0106 AC: 4 AN: 376

East Asian (EAS) AF: 0.195 AC: 177 AN: 910

South Asian (SAS) AF: 0.0201 AC: 35 AN: 1738

European-Finnish (FIN) AF: 0.0199 AC: 11 AN: 552

Middle Eastern (MID) AF: 0.0172 AC: 1 AN: 58

European-Non Finnish (NFE) AF: 0.00481 AC: 48 AN: 9978

Other (OTH) AF: 0.00937 AC: 8 AN: 854

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

African (AFR) AF: 0.00231 AC: 96 AN: 41566

American (AMR) AF: 0.0424 AC: 649 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00979 AC: 34 AN: 3472

East Asian (EAS) AF: 0.182 AC: 943 AN: 5188

South Asian (SAS) AF: 0.0240 AC: 116 AN: 4828

European-Finnish (FIN) AF: 0.0225 AC: 239 AN: 10610

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00331 AC: 225 AN: 68034

Other (OTH) AF: 0.0170 AC: 36 AN: 2116

Alfa AF: 0.0113 Hom.: 23

Bravo AF: 0.0178

Asia WGS AF: 0.0720 AC: 248 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.3
DANN	Benign	0.77
PhyloP100		0.31
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12233351; hg19: chr22-19117892;