16-1776301-G-T

Variant names:

• chr16-1776301-G-T
• rs2437732
• NM_001257370.2:c.*63G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 20 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
EME2	NM_001257370.2	c.*63G>T		3_prime_UTR_variant	Exon 8 of 8	ENST00000568449.7	NP_001244299.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EME2	ENST00000568449.7	c.*63G>T		3_prime_UTR_variant	Exon 8 of 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

African (AFR) AF: 0.179 AC: 5787 AN: 32254

American (AMR) AF: 0.645 AC: 26772 AN: 41494

Ashkenazi Jewish (ASJ) AF: 0.593 AC: 14011 AN: 23610

East Asian (EAS) AF: 0.281 AC: 10992 AN: 39084

South Asian (SAS) AF: 0.280 AC: 22771 AN: 81374

European-Finnish (FIN) AF: 0.487 AC: 24564 AN: 50458

Middle Eastern (MID) AF: 0.559 AC: 3092 AN: 5528

European-Non Finnish (NFE) AF: 0.581 AC: 622478 AN: 1072236

Other (OTH) AF: 0.520 AC: 30092 AN: 57902

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

African (AFR) AF: 0.185 AC: 7691 AN: 41524

American (AMR) AF: 0.558 AC: 8537 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.613 AC: 2129 AN: 3472

East Asian (EAS) AF: 0.323 AC: 1663 AN: 5154

South Asian (SAS) AF: 0.269 AC: 1298 AN: 4818

European-Finnish (FIN) AF: 0.471 AC: 4974 AN: 10556

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.576 AC: 39099 AN: 67924

Other (OTH) AF: 0.493 AC: 1041 AN: 2112

Alfa AF: 0.542 Hom.: 23259

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
PhyloP100		-0.23
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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

Other links and lift over

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