chr18-2847235-C-A

Variant names:

• chr18-2847235-C-A
• rs1180626147
• NM_032048.3:c.47C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032048.3(EMILIN2):​c.47C>A​(p.Ala16Glu) 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. 15/22 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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EMILIN2 NM_032048.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.642
• Publications: 0 publications found

Genes affected

EMILIN2 (HGNC:19881): (elastin microfibril interfacer 2) Predicted to enable extracellular matrix constituent conferring elasticity. Predicted to be involved in cell adhesion. Located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000289061 (HGNC:):

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=0.16982237).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032048.3. 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
	EMILIN2	NM_032048.3	MANE Select	c.47C>A	p.Ala16Glu	missense	Exon 1 of 8	NP_114437.2	Q9BXX0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMILIN2	ENST00000254528.4	TSL:1 MANE Select	c.47C>A	p.Ala16Glu	missense	Exon 1 of 8	ENSP00000254528.3	Q9BXX0
	EMILIN2	ENST00000942047.1		c.47C>A	p.Ala16Glu	missense	Exon 1 of 7	ENSP00000612106.1
	EMILIN2	ENST00000942046.1		c.47C>A	p.Ala16Glu	missense	Exon 1 of 7	ENSP00000612105.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1116288 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 537932

African (AFR) AF: 0.00 AC: 0 AN: 22520

American (AMR) AF: 0.00 AC: 0 AN: 9640

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14500

East Asian (EAS) AF: 0.00 AC: 0 AN: 25270

South Asian (SAS) AF: 0.00 AC: 0 AN: 33578

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23194

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2950

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 940604

Other (OTH) AF: 0.00 AC: 0 AN: 44032

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

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	0.31
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	19
DANN	Benign	0.71
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.073	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.64
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.11
Sift	Uncertain	0.024	D
Sift4G	Uncertain	0.029	D
Polyphen		0.65	P
Vest4		0.39
MutPred		0.44		Gain of loop (P = 0.0079)
MVP		0.22
MPC		0.098
ClinPred		0.65	D
GERP RS		1.6
PromoterAI		-0.019	Neutral
Varity_R		0.21
gMVP		0.58

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

dbSNP: rs1180626147; hg19: chr18-2847233;