2-106073912-G-A

Variant names:

• chr2-106073912-G-A
• rs10187689
• NM_032411.3:c.154G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032411.3(ECRG4):​c.154G>A​(p.Ala52Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00471 in 1,614,216 control chromosomes in the GnomAD database, including 252 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (135 hom., cov: 33)
  • Exomes 𝑓: 0.0029 (117 hom.)
• Consequence: ECRG4 NM_032411.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.49
• Publications: 7 publications found

Genes affected

ECRG4 (HGNC:24642): (ECRG4 augurin precursor) Enables neuropeptide hormone activity. Involved in neuropeptide signaling pathway; positive regulation of hormone secretion; and vasopressin secretion. Located in apical plasma membrane; dense core granule; and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0027790368).
• BP6: Variant 2-106073912-G-A is Benign according to our data. Variant chr2-106073912-G-A is described in ClinVar as Benign. ClinVar VariationId is 767812.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0714 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032411.3. 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
	ECRG4	NM_032411.3	MANE Select	c.154G>A	p.Ala52Thr	missense	Exon 3 of 4	NP_115787.1	Q9H1Z8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECRG4	ENST00000238044.8	TSL:1 MANE Select	c.154G>A	p.Ala52Thr	missense	Exon 3 of 4	ENSP00000238044.3	Q9H1Z8
	ECRG4	ENST00000437659.1	TSL:3	c.160G>A	p.Ala54Thr	missense	Exon 4 of 5	ENSP00000388664.1	C9JRR0
	ECRG4	ENST00000409944.5	TSL:5	c.46G>A	p.Ala16Thr	missense	Exon 4 of 5	ENSP00000386421.1	B8ZZE5

Frequencies

GnomAD3 genomes AF: 0.0220 AC: 3349 AN: 152212 Hom.: 135 Cov.: 33

Gnomad AFR AF: 0.0737

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0113

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000941

Gnomad OTH AF: 0.0225

GnomAD2 exomes AF: 0.00633 AC: 1592 AN: 251490 AF XY: 0.00491

Gnomad AFR exome AF: 0.0742

Gnomad AMR exome AF: 0.00460

Gnomad ASJ exome AF: 0.00397

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.00133

Gnomad OTH exome AF: 0.00440

GnomAD4 exome AF: 0.00291 AC: 4252 AN: 1461886 Hom.: 117 Cov.: 31 AF XY: 0.00265 AC XY: 1928 AN XY: 727242

African (AFR) AF: 0.0764 AC: 2558 AN: 33476

American (AMR) AF: 0.00512 AC: 229 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00383 AC: 100 AN: 26136

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.000243 AC: 21 AN: 86258

European-Finnish (FIN) AF: 0.000150 AC: 8 AN: 53420

Middle Eastern (MID) AF: 0.00468 AC: 27 AN: 5768

European-Non Finnish (NFE) AF: 0.000826 AC: 919 AN: 1112008

Other (OTH) AF: 0.00642 AC: 388 AN: 60396

GnomAD4 genome AF: 0.0220 AC: 3354 AN: 152330 Hom.: 135 Cov.: 33 AF XY: 0.0217 AC XY: 1618 AN XY: 74500

African (AFR) AF: 0.0736 AC: 3059 AN: 41572

American (AMR) AF: 0.0113 AC: 173 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00230 AC: 8 AN: 3472

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

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000941 AC: 64 AN: 68028

Other (OTH) AF: 0.0223 AC: 47 AN: 2112

Alfa AF: 0.00914 Hom.: 118

Bravo AF: 0.0248

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0697 AC: 307

ESP6500EA AF: 0.00140 AC: 12

ExAC AF: 0.00772 AC: 937

Asia WGS AF: 0.00751 AC: 26 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.00136

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.042	T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.73	T
MetaRNN	Benign	0.0028	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		3.5
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.11
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.023	D
Polyphen		0.86	P
Vest4		0.16
MVP		0.49
MPC		0.34
ClinPred		0.021	T
GERP RS		4.7
Varity_R		0.11
gMVP		0.46
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs10187689; hg19: chr2-106690368;