dbSNP rs12233351: ESS2:c.*3817A>G (chr22-19130379-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.308

Publications

3 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:

ENSG00000223461 (HGNC:):

ENSG00000223461 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
ESS2	NM_022719.3 link	c.*3817A>G	3_prime_UTR_variant	Exon 10 of 10	ENST00000252137.11	NP_073210.1
ESS2	NR_134304.2 link	n.5336A>G	non_coding_transcript_exon_variant	Exon 10 of 10
ESS2	XM_005261282.5 link	c.*3817A>G	3_prime_UTR_variant	Exon 10 of 10		XP_005261339.1
ESS2	XM_006724329.4 link	c.*3817A>G	3_prime_UTR_variant	Exon 10 of 10		XP_006724392.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ESS2	ENST00000252137.11 link	c.*3817A>G		3_prime_UTR_variant	Exon 10 of 10	1	NM_022719.3	ENSP00000252137.6
ENSG00000223461	ENST00000752497.1 link	n.146-4400T>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.0153

AC:

2332

AN:

152200

Hom.:

101

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.0194

AC XY:

172

AN XY:

8852

show subpopulations

African (AFR)

AF:

0.00360

AC:

AN:

278

American (AMR)

AF:

0.0518

AC:

AN:

328

Ashkenazi Jewish (ASJ)

AF:

0.0106

AC:

AN:

376

East Asian (EAS)

AF:

0.195

AC:

177

AN:

910

South Asian (SAS)

AF:

0.0201

AC:

AN:

1738

European-Finnish (FIN)

AF:

0.0199

AC:

AN:

552

Middle Eastern (MID)

AF:

0.0172

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00481

AC:

AN:

9978

Other (OTH)

AF:

0.00937

AC:

AN:

854

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0154

AC:

2343

AN:

152318

Hom.:

103

Cov.:

AF XY:

0.0180

AC XY:

1341

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.00231

AC:

AN:

41566

American (AMR)

AF:

0.0424

AC:

649

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00979

AC:

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.00331

AC:

225

AN:

68034

Other (OTH)

AF:

0.0170

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

107

214

321

428

535

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0113

Hom.:

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

(source)

DANN

Benign

0.77

PhyloP100

0.31

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over