Genetic Variant 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

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:

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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	UniProt
ESS2	NM_022719.3 link	c.*3817A>G	3_prime_UTR_variant	Exon 10 of 10	ENST00000252137.11	NP_073210.1	Q96DF8
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
ESS2	NR_134304.2 link	n.5336A>G	non_coding_transcript_exon_variant	Exon 10 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ESS2	ENST00000252137 link	c.*3817A>G		3_prime_UTR_variant	Exon 10 of 10	1	NM_022719.3	ENSP00000252137.6		Q96DF8

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

Gnomad4 AFR exome

AF:

0.00360

AC:

AN:

278

Gnomad4 AMR exome

AF:

0.0518

AC:

AN:

328

Gnomad4 ASJ exome

AF:

0.0106

AC:

AN:

376

Gnomad4 EAS exome

AF:

0.195

AC:

177

AN:

910

Gnomad4 SAS exome

AF:

0.0201

AC:

AN:

1738

Gnomad4 FIN exome

AF:

0.0199

AC:

AN:

552

Gnomad4 NFE exome

AF:

0.00481

AC:

AN:

9978

Gnomad4 Remaining exome

AF:

0.00937

AC:

AN:

854

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Gnomad4 AFR

AF:

0.00231

AC:

0.00230958

AN:

0.00230958

Gnomad4 AMR

AF:

0.0424

AC:

0.0424238

AN:

0.0424238

Gnomad4 ASJ

AF:

0.00979

AC:

0.00979263

AN:

0.00979263

Gnomad4 EAS

AF:

0.182

AC:

0.181766

AN:

0.181766

Gnomad4 SAS

AF:

0.0240

AC:

0.0240265

AN:

0.0240265

Gnomad4 FIN

AF:

0.0225

AC:

0.0225259

AN:

0.0225259

Gnomad4 NFE

AF:

0.00331

AC:

0.00330717

AN:

0.00330717

Gnomad4 OTH

AF:

0.0170

AC:

0.0170132

AN:

0.0170132

Heterozygous variant carriers

107

214

321

428

535

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

DANN

Benign

0.77

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over