chr3-55888403-C-G

Variant names:

• chr3-55888403-C-G
• NM_015576.3:c.2550G>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_015576.3(ERC2):​c.2550G>C​(p.Glu850Asp) 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 pathogenic 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.45
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.816

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERC2	NM_015576.3	c.2550G>C	p.Glu850Asp	missense_variant	Exon 14 of 18	ENST00000288221.11	NP_056391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERC2	ENST00000288221.11	c.2550G>C	p.Glu850Asp	missense_variant	Exon 14 of 18	1	NM_015576.3	ENSP00000288221.6
ERC2	ENST00000460849.5	n.2550G>C		non_coding_transcript_exon_variant	Exon 14 of 19	1		ENSP00000417445.1
ERC2	ENST00000492584.3	c.2574G>C	p.Glu858Asp	missense_variant	Exon 14 of 18	5		ENSP00000417280.3

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

Submissions by phenotype

not specified Uncertain:1

Feb 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2550G>C (p.E850D) alteration is located in exon 14 (coding exon 13) of the ERC2 gene. This alteration results from a G to C substitution at nucleotide position 2550, causing the glutamic acid (E) at amino acid position 850 to be replaced by an aspartic acid (D). 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	Uncertain	0.53
BayesDel_addAF	Uncertain	0.091	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T;T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Pathogenic	0.98	.;D
M_CAP	Benign	0.040	D
MetaRNN	Pathogenic	0.82	D;D
MetaSVM	Benign	-0.44	T
MutationAssessor	Uncertain	2.8	M;M
PhyloP100		1.4
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-2.1	N;.
REVEL	Uncertain	0.32
Sift	Uncertain	0.010	D;.
Sift4G	Uncertain	0.018	D;D
Polyphen		0.98	D;D
Vest4		0.79
MutPred		0.67		Loss of methylation at K846 (P = 0.1237);Loss of methylation at K846 (P = 0.1237);
MVP		0.43
MPC		1.1
ClinPred		0.96	D
GERP RS		4.0
Varity_R		0.40
gMVP		0.53
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

hg19: chr3-55922431;