3-55992142-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015576.3(ERC2):​c.2170G>A​(p.Ala724Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 32)

Consequence

ERC2
NM_015576.3 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.47
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.16875672).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ERC2NM_015576.3 linkc.2170G>A p.Ala724Thr missense_variant Exon 11 of 18 ENST00000288221.11 NP_056391.1 O15083

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ERC2ENST00000288221.11 linkc.2170G>A p.Ala724Thr missense_variant Exon 11 of 18 1 NM_015576.3 ENSP00000288221.6 O15083
ERC2ENST00000460849.5 linkn.2170G>A non_coding_transcript_exon_variant Exon 11 of 19 1 ENSP00000417445.1 O15083
ERC2ENST00000492584.3 linkc.2206G>A p.Ala736Thr missense_variant Exon 12 of 18 5 ENSP00000417280.3 H7C4G9

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 07, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2170G>A (p.A724T) alteration is located in exon 11 (coding exon 10) of the ERC2 gene. This alteration results from a G to A substitution at nucleotide position 2170, causing the alanine (A) at amino acid position 724 to be replaced by a threonine (T). 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
0.080
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.53
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.096
T;T
Eigen
Benign
-0.068
Eigen_PC
Benign
0.13
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Uncertain
0.92
.;D
M_CAP
Benign
0.0076
T
MetaRNN
Benign
0.17
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.1
L;L
PrimateAI
Uncertain
0.68
T
PROVEAN
Benign
-1.1
N;.
REVEL
Benign
0.083
Sift
Benign
0.24
T;.
Sift4G
Benign
0.082
T;T
Polyphen
0.0030
B;B
Vest4
0.27
MutPred
0.38
Gain of phosphorylation at A724 (P = 0.0357);Gain of phosphorylation at A724 (P = 0.0357);
MVP
0.15
MPC
0.35
ClinPred
0.82
D
GERP RS
5.7
Varity_R
0.17
gMVP
0.54

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-56026170; API