Genetic Variant NM_033266.4:c.2043C>A (chr16-23694785-G-T) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_033266.4(ERN2):c.2043C>A(p.Pro681Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000049 in 1,613,098 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

ERN2
NM_033266.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -8.50

Publications

0 publications found

Variant links:

Genes affected

ERN2 (HGNC:16942): (endoplasmic reticulum to nucleus signaling 2) Enables several functions, including ATP binding activity; magnesium ion binding activity; and protein serine/threonine kinase activity. Involved in several processes, including apoptotic chromosome condensation; negative regulation of transcription, DNA-templated; and rRNA catabolic process. Predicted to be located in endoplasmic reticulum membrane and endoplasmic reticulum quality control compartment. Predicted to be integral component of membrane. Predicted to be part of IRE1-TRAF2-ASK1 complex. [provided by Alliance of Genome Resources, Apr 2022]

ERN2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 16-23694785-G-T is Benign according to our data. Variant chr16-23694785-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 736799.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-8.5 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033266.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERN2	NM_033266.4	MANE Select	c.2043C>A	p.Pro681Pro	synonymous	Exon 17 of 22	NP_150296.4
	ERN2	NM_001308220.2		c.1887C>A	p.Pro629Pro	synonymous	Exon 16 of 21	NP_001295149.2	E7ETG2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ERN2	ENST00000256797.9	TSL:1 MANE Select	c.2043C>A	p.Pro681Pro	synonymous	Exon 17 of 22	ENSP00000256797.5	Q76MJ5
ERN2	ENST00000457008.6	TSL:1	c.1887C>A	p.Pro629Pro	synonymous	Exon 16 of 21	ENSP00000413812.2	E7ETG2
ERN2	ENST00000885430.1		c.2073C>A	p.Pro691Pro	synonymous	Exon 18 of 23	ENSP00000555489.1

Frequencies

GnomAD3 genomes

AF:

0.000263

AC:

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000916

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000808

AC:

AN:

247454

AF XY:

0.0000447

show subpopulations

Gnomad AFR exome

AF:

0.00108

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000897

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.0000253

AC:

AN:

1460736

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

726594

show subpopulations

African (AFR)

AF:

0.000896

AC:

AN:

33474

American (AMR)

AF:

0.00

AC:

AN:

44632

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26100

East Asian (EAS)

AF:

0.00

AC:

AN:

39668

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86034

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53114

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5730

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111678

Other (OTH)

AF:

0.0000995

AC:

AN:

60306

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.000276

AC:

AN:

152362

Hom.:

Cov.:

AF XY:

0.000295

AC XY:

AN XY:

74510

show subpopulations

African (AFR)

AF:

0.000962

AC:

AN:

41592

American (AMR)

AF:

0.000131

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Alfa

AF:

0.000102

Hom.:

Bravo

AF:

0.000355

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.0070

(source)

DANN

Benign

0.84

PhyloP100

-8.5

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over