2-55867066-GA-G

Variant names:

• chr2-55867066-GA-G
• rs200536754
• NM_001039348.3:c.*6delT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001039348.3(EFEMP1):​c.*6delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0261 in 1,612,118 control chromosomes in the GnomAD database, including 958 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (54 hom., cov: 32)
  • Exomes 𝑓: 0.027 (904 hom.)
• Consequence: EFEMP1 NM_001039348.3 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts U:1 B:4
• Conservation: PhyloP100: 0.340

Genes affected

EFEMP1 (HGNC:3218): (EGF containing fibulin extracellular matrix protein 1) This gene encodes a member of the fibulin family of extracellular matrix glycoproteins. Like all members of this family, the encoded protein contains tandemly repeated epidermal growth factor-like repeats followed by a C-terminus fibulin-type domain. This gene is upregulated in malignant gliomas and may play a role in the aggressive nature of these tumors. Mutations in this gene are associated with Doyne honeycomb retinal dystrophy. Alternatively spliced transcript variants that encode the same protein have been described.[provided by RefSeq, Nov 2009]

LOC112268416 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 2-55867066-GA-G is Benign according to our data. Variant chr2-55867066-GA-G is described in ClinVar as [Likely_benign]. Clinvar id is 191301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-55867066-GA-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.075 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFEMP1	NM_001039348.3	c.*6delT		3_prime_UTR_variant	Exon 12 of 12	ENST00000355426.8	NP_001034437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EFEMP1	ENST00000355426	c.*6delT		3_prime_UTR_variant	Exon 12 of 12	1	NM_001039348.3	ENSP00000347596.3

Frequencies

GnomAD3 genomes AF: 0.0196 AC: 2973 AN: 152026 Hom.: 55 Cov.: 32

Gnomad AFR AF: 0.00459

Gnomad AMI AF: 0.0297

Gnomad AMR AF: 0.0130

Gnomad ASJ AF: 0.0675

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0816

Gnomad FIN AF: 0.0187

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0243

Gnomad OTH AF: 0.0283

GnomAD2 exomes AF: 0.0290 AC: 7277 AN: 251226 AF XY: 0.0332

Gnomad AFR exome AF: 0.00425

Gnomad AMR exome AF: 0.0111

Gnomad ASJ exome AF: 0.0703

Gnomad EAS exome AF: 0.000489

Gnomad FIN exome AF: 0.0158

Gnomad NFE exome AF: 0.0261

Gnomad OTH exome AF: 0.0359

GnomAD4 exome AF: 0.0268 AC: 39169 AN: 1459974 Hom.: 904 Cov.: 30 AF XY: 0.0291 AC XY: 21106 AN XY: 726300

Gnomad4 AFR exome AF: 0.00362 AC: 121 AN: 33428

Gnomad4 AMR exome AF: 0.0124 AC: 553 AN: 44716

Gnomad4 ASJ exome AF: 0.0689 AC: 1800 AN: 26126

Gnomad4 EAS exome AF: 0.000277 AC: 11 AN: 39684

Gnomad4 SAS exome AF: 0.0865 AC: 7452 AN: 86182

Gnomad4 FIN exome AF: 0.0173 AC: 925 AN: 53400

Gnomad4 NFE exome AF: 0.0235 AC: 26100 AN: 1111760

Gnomad4 Remaining exome AF: 0.0305 AC: 1835 AN: 60234

GnomAD4 genome AF: 0.0195 AC: 2972 AN: 152144 Hom.: 54 Cov.: 32 AF XY: 0.0205 AC XY: 1524 AN XY: 74400

Gnomad4 AFR AF: 0.00458 AC: 0.00457501 AN: 0.00457501

Gnomad4 AMR AF: 0.0130 AC: 0.0129768 AN: 0.0129768

Gnomad4 ASJ AF: 0.0675 AC: 0.067513 AN: 0.067513

Gnomad4 EAS AF: 0.000771 AC: 0.00077101 AN: 0.00077101

Gnomad4 SAS AF: 0.0817 AC: 0.0817048 AN: 0.0817048

Gnomad4 FIN AF: 0.0187 AC: 0.0186863 AN: 0.0186863

Gnomad4 NFE AF: 0.0243 AC: 0.0243293 AN: 0.0243293

Gnomad4 OTH AF: 0.0275 AC: 0.0275142 AN: 0.0275142

Alfa AF: 0.0305 Hom.: 15

Bravo AF: 0.0182

Asia WGS AF: 0.0350 AC: 124 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Uncertain:1 Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Jun 03, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 28, 2016

Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: research

- -

Retinal dystrophy Uncertain:1

Jan 01, 2010

Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Doyne honeycomb retinal dystrophy Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Nov 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mutation Taster		=100/0	polymorphism (auto)

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

Publications

LitVar

Other links and lift over

dbSNP: rs200536754; hg19: chr2-56094201; COSMIC: COSV62614759;