9-95876046-C-A

Variant names:

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>A(p.Pro3Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00877 in 1,588,756 control chromosomes in the GnomAD database, including 78 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0061 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0091 ( 72 hom. )

Consequence

ERCC6L2
NM_020207.7 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.09

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=0.0025633276).

BP6

Variant 9-95876046-C-A is Benign according to our data. Variant chr9-95876046-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1166945.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00614 (935/152346) while in subpopulation NFE AF= 0.00947 (644/68022). AF 95% confidence interval is 0.00886. There are 6 homozygotes in gnomad4. There are 454 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERCC6L2	NM_020207.7 link	c.8C>A	p.Pro3Gln	missense_variant	Exon 1 of 19	ENST00000653738.2	NP_064592.3	Q5T890

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERCC6L2	ENST00000653738.2 link	c.8C>A	p.Pro3Gln	missense_variant	Exon 1 of 19		NM_020207.7	ENSP00000499221.2		A0A590UJ07

Frequencies

GnomAD3 genomes

AF:

0.00614

AC:

935

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00133

Gnomad AMI

AF:

0.00220

Gnomad AMR

AF:

0.00268

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0163

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00947

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00618

AC:

1261

AN:

203882

Hom.:

AF XY:

0.00581

AC XY:

645

AN XY:

110928

show subpopulations

Gnomad AFR exome

AF:

0.00165

Gnomad AMR exome

AF:

0.00156

Gnomad ASJ exome

AF:

0.00354

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000457

Gnomad FIN exome

AF:

0.0168

Gnomad NFE exome

AF:

0.00938

Gnomad OTH exome

AF:

0.00484

GnomAD4 exome

AF:

0.00905

AC:

13006

AN:

1436410

Hom.:

Cov.:

AF XY:

0.00857

AC XY:

6106

AN XY:

712436

show subpopulations

Gnomad4 AFR exome

AF:

0.00110

Gnomad4 AMR exome

AF:

0.00151

Gnomad4 ASJ exome

AF:

0.00352

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000643

Gnomad4 FIN exome

AF:

0.0163

Gnomad4 NFE exome

AF:

0.0105

Gnomad4 OTH exome

AF:

0.00697

GnomAD4 genome

AF:

0.00614

AC:

935

AN:

152346

Hom.:

Cov.:

AF XY:

0.00609

AC XY:

454

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.00132

Gnomad4 AMR

AF:

0.00268

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.0163

Gnomad4 NFE

AF:

0.00947

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00735

Hom.:

Bravo

AF:

0.00504

TwinsUK

AF:

0.00917

AC:

ALSPAC

AF:

0.00856

AC:

ESP6500AA

AF:

0.00162

AC:

ESP6500EA

AF:

0.00856

AC:

ExAC

AF:

0.00565

AC:

677

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Dec 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ERCC6L2: BP4, BS1, BS2 -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Pancytopenia-developmental delay syndrome

Benign:1

Sep 30, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Jun 21, 2021

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

ERCC6L2-related disorder

Benign:1

Apr 30, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.15

CADD

Benign

6.9

DANN

Benign

0.84

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0019

LIST_S2

Benign

0.34

MetaRNN

Benign

0.0026

MetaSVM

Benign

-0.74

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.070

REVEL

Uncertain

0.33

Sift

Benign

0.053

Sift4G

Benign

0.12

Vest4

0.11

MVP

0.25

MPC

0.20

ClinPred

0.0084

GERP RS

-3.1

gMVP

0.17

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