Variant 3-56010537-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_015576.3(ERC2):c.1832G>A(p.Arg611Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000137 in 1,461,354 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

ERC2
NM_015576.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.13

Variant links:

Genes affected

ERC2 (HGNC:31922): (ELKS/RAB6-interacting/CAST family member 2) This gene encodes a protein that belongs to the Rab3-interacting molecule (RIM)-binding protein family. Members of this protein family form part of the cytomatrix at the active zone (CAZ) complex and function as regulators of neurotransmitter release. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2015]

ERC2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13436419).

BS2

High AC in GnomAdExome4 at 20 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERC2	NM_015576.3 link	c.1832G>A	p.Arg611Lys	missense_variant	9/18	ENST00000288221.11	NP_056391.1	O15083

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ERC2	ENST00000288221.11 link	c.1832G>A	p.Arg611Lys	missense_variant	9/18	1	NM_015576.3	ENSP00000288221.6	O15083
ERC2	ENST00000460849.5 link	n.1832G>A		non_coding_transcript_exon_variant	9/19	1		ENSP00000417445.1	O15083
ERC2	ENST00000492584.3 link	c.1832G>A	p.Arg611Lys	missense_variant	9/18	5		ENSP00000417280.3	H7C4G9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000137

AC:

AN:

1461354

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

726946

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000171

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000579

Hom.:

Bravo

AF:

0.00000378

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 16, 2024

The c.1832G>A (p.R611K) alteration is located in exon 9 (coding exon 8) of the ERC2 gene. This alteration results from a G to A substitution at nucleotide position 1832, causing the arginine (R) at amino acid position 611 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Pathogenic

DANN

Benign

0.88

DEOGEN2

Benign

0.041

T;T

Eigen

Benign

-0.28

Eigen_PC

Benign

0.028

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.81

.;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.79

N;N

PrimateAI

Uncertain

0.76

PROVEAN

Benign

0.10

N;.

REVEL

Benign

0.15

Sift

Benign

1.0

T;.

Sift4G

Benign

0.81

T;T

Polyphen

0.0020

B;B

Vest4

0.40

MutPred

0.39

Gain of ubiquitination at R611 (P = 0.009);Gain of ubiquitination at R611 (P = 0.009);

MVP

0.15

MPC

0.35

ClinPred

0.87

GERP RS

6.0

Varity_R

0.31

gMVP

0.88

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over