16-23691422-C-T

Variant names:

• chr16-23691422-C-T
• rs144279415
• NM_033266.4:c.2380G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_033266.4(ERN2):​c.2380G>A​(p.Val794Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000369 in 1,598,770 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00017 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: ERN2 NM_033266.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.86
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13742667).

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.2380G>A	p.Val794Ile	missense	Exon 20 of 22	NP_150296.4
	ERN2	NM_001308220.2		c.2224G>A	p.Val742Ile	missense	Exon 19 of 21	NP_001295149.2	E7ETG2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERN2	ENST00000256797.9	TSL:1 MANE Select	c.2380G>A	p.Val794Ile	missense	Exon 20 of 22	ENSP00000256797.5	Q76MJ5
	ERN2	ENST00000457008.6	TSL:1	c.2224G>A	p.Val742Ile	missense	Exon 19 of 21	ENSP00000413812.2	E7ETG2
	ERN2	ENST00000885430.1		c.2410G>A	p.Val804Ile	missense	Exon 21 of 23	ENSP00000555489.1

Frequencies

GnomAD3 genomes AF: 0.000171 AC: 26 AN: 152224 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000579

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000550 AC: 13 AN: 236578 AF XY: 0.0000465

Gnomad AFR exome AF: 0.000449

Gnomad AMR exome AF: 0.0000584

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000899

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000228 AC: 33 AN: 1446428 Hom.: 0 Cov.: 33 AF XY: 0.0000278 AC XY: 20 AN XY: 719960

African (AFR) AF: 0.000359 AC: 12 AN: 33452

American (AMR) AF: 0.0000448 AC: 2 AN: 44596

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26102

East Asian (EAS) AF: 0.00 AC: 0 AN: 39656

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86016

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39048

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000720 AC: 8 AN: 1111516

Other (OTH) AF: 0.0000166 AC: 1 AN: 60278

GnomAD4 genome AF: 0.000171 AC: 26 AN: 152342 Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11 AN XY: 74488

African (AFR) AF: 0.000577 AC: 24 AN: 41580

American (AMR) AF: 0.00 AC: 0 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000939 Hom.: 0

Bravo AF: 0.000185

ESP6500AA AF: 0.000455 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000494 AC: 6

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000595

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.53
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.090	T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.57	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		3.9
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.86	N
REVEL	Benign	0.15
Sift	Benign	0.082	T
Sift4G	Benign	0.068	T
Polyphen		0.16	B
Vest4		0.27
MVP		0.65
MPC		0.16
ClinPred		0.11	T
GERP RS		4.7
Varity_R		0.25
gMVP		0.46
Mutation Taster		=73/27	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs144279415; hg19: chr16-23702743; COSMIC: COSV99892371; COSMIC: COSV99892371;