Variant 9-95876031-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_020207.7(ERCC6L2):c.-8C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00233 in 1,588,360 control chromosomes in the GnomAD database, including 68 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0031 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 63 hom. )

Consequence

ERCC6L2
NM_020207.7 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.100

Variant links:

Genes affected

ERCC6L2 (HGNC:26922): (ERCC excision repair 6 like 2) This gene encodes a member of the Snf2 family of helicase-like proteins. The encoded protein may play a role in DNA repair and mitochondrial function. Mutations in this gene have been associated with bone marrow failure syndrome 2. Alternatively spliced transcript variants that encode different protein isoforms have been described. [provided by RefSeq, Apr 2014]

ERCC6L2 links:

ERCC6L2-AS1 (HGNC:27858): (ERCC6L2 antisense RNA 1)

ERCC6L2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0030474067).

BP6

Variant 9-95876031-C-G is Benign according to our data. Variant chr9-95876031-C-G is described in ClinVar as [Benign]. Clinvar id is 732858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00308 (469/152370) while in subpopulation EAS AF= 0.0353 (183/5186). AF 95% confidence interval is 0.0311. There are 5 homozygotes in gnomad4. There are 324 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERCC6L2	NM_020207.7 linkuse as main transcript	c.-8C>G		5_prime_UTR_variant	1/19	ENST00000653738.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERCC6L2	ENST00000653738.2 linkuse as main transcript	c.-8C>G		5_prime_UTR_variant	1/19		NM_020207.7	P2

Frequencies

GnomAD3 genomes

AF:

0.00308

AC:

469

AN:

152252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0352

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.0216

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000705

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00410

AC:

840

AN:

204736

Hom.:

AF XY:

0.00390

AC XY:

435

AN XY:

111554

show subpopulations

Gnomad AFR exome

AF:

0.0000877

Gnomad AMR exome

AF:

0.0000324

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0285

Gnomad SAS exome

AF:

0.000989

Gnomad FIN exome

AF:

0.0183

Gnomad NFE exome

AF:

0.000572

Gnomad OTH exome

AF:

0.00154

GnomAD4 exome

AF:

0.00225

AC:

3233

AN:

1435990

Hom.:

Cov.:

AF XY:

0.00220

AC XY:

1567

AN XY:

712224

show subpopulations

Gnomad4 AFR exome

AF:

0.0000305

Gnomad4 AMR exome

AF:

0.0000239

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0517

Gnomad4 SAS exome

AF:

0.00115

Gnomad4 FIN exome

AF:

0.0180

Gnomad4 NFE exome

AF:

0.000157

Gnomad4 OTH exome

AF:

0.00167

GnomAD4 genome

AF:

0.00308

AC:

469

AN:

152370

Hom.:

Cov.:

AF XY:

0.00435

AC XY:

324

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0353

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.0216

Gnomad4 NFE

AF:

0.000705

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00122

Hom.:

Bravo

AF:

0.00143

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000118

AC:

ExAC

AF:

0.00343

AC:

411

Asia WGS

AF:

0.0100

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Sep 08, 2020

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 16, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.11

Cadd

Benign

Dann

Uncertain

0.99

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0036

LIST_S2

Benign

0.34

MetaRNN

Benign

0.0030

MetaSVM

Benign

-0.81

MutationTaster

Benign

1.0

PrimateAI

Benign

0.44

PROVEAN

Benign

0.28

REVEL

Benign

0.17

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.049

Vest4

0.27

MVP

0.29

MPC

0.34

ClinPred

0.029

GERP RS

-1.7

gMVP

0.19

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over