18-2885112-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_032048.3(EMILIN2):c.406C>T(p.Pro136Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00201 in 1,609,258 control chromosomes in the GnomAD database, including 70 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (37 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (33 hom.)
• Consequence: EMILIN2 NM_032048.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.10

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0052028).
• BP6: Variant 18-2885112-C-T is Benign according to our data. Variant chr18-2885112-C-T is described in ClinVar as [Benign]. Clinvar id is 781394.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0108 (1646/152294) while in subpopulation AFR AF= 0.0363 (1507/41566). AF 95% confidence interval is 0.0347. There are 37 homozygotes in gnomad4. There are 759 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 37 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EMILIN2	NM_032048.3	c.406C>T	p.Pro136Ser	missense_variant	3/8	ENST00000254528.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EMILIN2	ENST00000254528.4	c.406C>T	p.Pro136Ser	missense_variant	3/8	1	NM_032048.3	P1

Frequencies

GnomAD3 genomes AF: 0.0108 AC: 1648 AN: 152176 Hom.: 37 Cov.: 33

Gnomad AFR AF: 0.0364

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.00511

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000220

Gnomad OTH AF: 0.0139

GnomAD3 exomes AF: 0.00297 AC: 732 AN: 246222 Hom.: 17 AF XY: 0.00220 AC XY: 293 AN XY: 133300

Gnomad AFR exome AF: 0.0384

Gnomad AMR exome AF: 0.00267

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000116

Gnomad OTH exome AF: 0.00168

GnomAD4 exome AF: 0.00109 AC: 1593 AN: 1456964 Hom.: 33 Cov.: 30 AF XY: 0.000934 AC XY: 677 AN XY: 724762

Gnomad4 AFR exome AF: 0.0366

Gnomad4 AMR exome AF: 0.00296

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000351

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000829

Gnomad4 OTH exome AF: 0.00251

GnomAD4 genome AF: 0.0108 AC: 1646 AN: 152294 Hom.: 37 Cov.: 33 AF XY: 0.0102 AC XY: 759 AN XY: 74474

Gnomad4 AFR AF: 0.0363

Gnomad4 AMR AF: 0.00510

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000221

Gnomad4 OTH AF: 0.0137

Alfa AF: 0.00189 Hom.: 9

Bravo AF: 0.0131

ESP6500AA AF: 0.0386 AC: 170

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00357 AC: 433

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.56
Cadd	Uncertain	24
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.81	T
MetaRNN	Benign	0.0052	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.7	M
MutationTaster	Benign	0.97	D
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.14
Sift	Uncertain	0.025	D
Sift4G	Uncertain	0.037	D
Polyphen		0.99	D
Vest4		0.18
MVP		0.58
MPC		0.47
ClinPred		0.022	T
GERP RS		5.8
Varity_R		0.16
gMVP		0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs35201788; hg19: chr18-2885110;