18-2847235-C-G

Variant names:

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

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>G​(p.Ala16Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000896 in 1,116,288 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A16E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 9.0e-7 (0 hom.)
• Consequence: EMILIN2 NM_032048.3 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.12694257).

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>G	p.Ala16Gly	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>G	p.Ala16Gly	missense	Exon 1 of 8	ENSP00000254528.3	Q9BXX0
	EMILIN2	ENST00000942047.1		c.47C>G	p.Ala16Gly	missense	Exon 1 of 7	ENSP00000612106.1
	EMILIN2	ENST00000942046.1		c.47C>G	p.Ala16Gly	missense	Exon 1 of 7	ENSP00000612105.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.96e-7 AC: 1 AN: 1116288 Hom.: 0 Cov.: 31 AF XY: 0.00000186 AC XY: 1 AN XY: 537932

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

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: 0.0000298 AC: 1 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

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	21
DANN	Benign	0.91
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.069	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.64
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.51	N
REVEL	Benign	0.037
Sift	Uncertain	0.027	D
Sift4G	Uncertain	0.010	D
Polyphen		0.65	P
Vest4		0.23
MutPred		0.30		Gain of loop (P = 0.0045)
MVP		0.13
MPC		0.084
ClinPred		0.41	T
GERP RS		1.6
PromoterAI		0.013	Neutral
Varity_R		0.086
gMVP		0.38

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;