16-10532759-T-TTTTTC

Position:

• chr16-10532759-T-TTTTTC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001424.6(EMP2):​c.*145_*146insGAAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00737 in 124,932 control chromosomes in the GnomAD database, including 105 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (59 hom., cov: 24)
  • Exomes 𝑓: 0.0024 (46 hom.)
• Consequence: EMP2 NM_001424.6 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0420

Genes affected

EMP2 (HGNC:3334): (epithelial membrane protein 2) This gene encodes a tetraspan protein of the PMP22/EMP family. The encoded protein regulates cell membrane composition. It has been associated with various functions including endocytosis, cell signaling, cell proliferation, cell migration, cell adhesion, cell death, cholesterol homeostasis, urinary albumin excretion, and embryo implantation. It is known to negatively regulate caveolin-1, a scaffolding protein which is the main component of the caveolae plasma membrane invaginations found in most cell types. Through activation of PTK2 it positively regulates vascular endothelial growth factor A. It also modulates the function of specific integrin isomers in the plasma membrane. Up-regulation of this gene has been linked to cancer progression in multiple different tissues. Mutations in this gene have been associated with nephrotic syndrome type 10 (NPHS10). [provided by RefSeq, Mar 2015]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 16-10532759-T-TTTTTC is Benign according to our data. Variant chr16-10532759-T-TTTTTC is described in ClinVar as [Likely_benign]. Clinvar id is 1706774.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0124 (769/61910) while in subpopulation AFR AF= 0.0225 (278/12330). AF 95% confidence interval is 0.0204. There are 59 homozygotes in gnomad4. There are 338 alleles in male gnomad4 subpopulation. Median coverage is 24. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 59 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EMP2	NM_001424.6	c.*145_*146insGAAAA		3_prime_UTR_variant	5/5	ENST00000359543.8	NP_001415.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EMP2	ENST00000359543	c.*145_*146insGAAAA		3_prime_UTR_variant	5/5	1	NM_001424.6	ENSP00000352540.3

Frequencies

GnomAD3 genomes AF: 0.0124 AC: 769 AN: 61898 Hom.: 59 Cov.: 24

Gnomad AFR AF: 0.0226

Gnomad AMI AF: 0.0223

Gnomad AMR AF: 0.00668

Gnomad ASJ AF: 0.00865

Gnomad EAS AF: 0.0164

Gnomad SAS AF: 0.0120

Gnomad FIN AF: 0.00746

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0103

Gnomad OTH AF: 0.0110

GnomAD4 exome AF: 0.00241 AC: 152 AN: 63022 Hom.: 46 Cov.: 3 AF XY: 0.00252 AC XY: 79 AN XY: 31366

Gnomad4 AFR exome AF: 0.00158

Gnomad4 AMR exome AF: 0.00166

Gnomad4 ASJ exome AF: 0.00231

Gnomad4 EAS exome AF: 0.000695

Gnomad4 SAS exome AF: 0.00880

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00268

Gnomad4 OTH exome AF: 0.00159

GnomAD4 genome AF: 0.0124 AC: 769 AN: 61910 Hom.: 59 Cov.: 24 AF XY: 0.0116 AC XY: 338 AN XY: 29062

Gnomad4 AFR AF: 0.0225

Gnomad4 AMR AF: 0.00667

Gnomad4 ASJ AF: 0.00865

Gnomad4 EAS AF: 0.0165

Gnomad4 SAS AF: 0.0121

Gnomad4 FIN AF: 0.00746

Gnomad4 NFE AF: 0.0103

Gnomad4 OTH AF: 0.0109

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 21, 2021

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1491247188; hg19: chr16-10626616;