NM_015576.3:c.2170G>A

Variant names:

• chr3-55992142-C-T
• NM_015576.3:c.2170G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_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. 13/22 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.47
• 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 0 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015576.3. 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
	ERC2	NM_015576.3	MANE Select	c.2170G>A	p.Ala724Thr	missense	Exon 11 of 18	NP_056391.1	O15083
	ERC2	NR_132749.2		n.2530G>A		non_coding_transcript_exon	Exon 11 of 19

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERC2	ENST00000288221.11	TSL:1 MANE Select	c.2170G>A	p.Ala724Thr	missense	Exon 11 of 18	ENSP00000288221.6	O15083
	ERC2	ENST00000460849.5	TSL:1	n.2170G>A		non_coding_transcript_exon	Exon 11 of 19	ENSP00000417445.1	O15083
	ERC2	ENST00000940588.1		c.2212G>A	p.Ala738Thr	missense	Exon 12 of 18	ENSP00000610647.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	0.080
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.096	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
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		2.5
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.083
Sift	Benign	0.24	T
Sift4G	Benign	0.082	T
Polyphen		0.0030	B
Vest4		0.27
MutPred		0.38		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
Mutation Taster		=85/15	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: chr3-56026170;