16-1776301-G-T

Position:

• chr16-1776301-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001257370.2(EME2):​c.*63G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 1,555,992 control chromosomes in the GnomAD database, including 231,827 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.44 (17362 hom., cov: 33)
  • Exomes 𝑓: 0.54 (214465 hom.)
• Consequence: EME2 NM_001257370.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.232

Genes affected

EME2 (HGNC:27289): (essential meiotic structure-specific endonuclease subunit 2) EME2 forms a heterodimer with MUS81 (MIM 606591) that functions as an XPF (MIM 278760)-type flap/fork endonuclease in DNA repair (Ciccia et al., 2007 [PubMed 17289582]).[supplied by OMIM, Mar 2008]

EME2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EME2	NM_001257370.2	c.*63G>T		3_prime_UTR_variant	8/8	ENST00000568449.7	NP_001244299.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EME2	ENST00000568449.7	c.*63G>T		3_prime_UTR_variant	8/8	1	NM_001257370.2	ENSP00000457353.1

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67341 AN: 151934 Hom.: 17360 Cov.: 33

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.792

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.498

GnomAD4 exome AF: 0.542 AC: 760559 AN: 1403940 Hom.: 214465 Cov.: 25 AF XY: 0.534 AC XY: 371001 AN XY: 694612

Gnomad4 AFR exome AF: 0.179

Gnomad4 AMR exome AF: 0.645

Gnomad4 ASJ exome AF: 0.593

Gnomad4 EAS exome AF: 0.281

Gnomad4 SAS exome AF: 0.280

Gnomad4 FIN exome AF: 0.487

Gnomad4 NFE exome AF: 0.581

Gnomad4 OTH exome AF: 0.520

GnomAD4 genome AF: 0.443 AC: 67351 AN: 152052 Hom.: 17362 Cov.: 33 AF XY: 0.436 AC XY: 32387 AN XY: 74310

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.558

Gnomad4 ASJ AF: 0.613

Gnomad4 EAS AF: 0.323

Gnomad4 SAS AF: 0.269

Gnomad4 FIN AF: 0.471

Gnomad4 NFE AF: 0.576

Gnomad4 OTH AF: 0.493

Alfa AF: 0.541 Hom.: 20056

Bravo AF: 0.450

Asia WGS AF: 0.291 AC: 1011 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.18
DANN	Benign	0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2437732; hg19: chr16-1826302; COSMIC: COSV51603109; COSMIC: COSV51603109;