Genetic Variant NM_020207.7:c.-15C>T (chr9-95876024-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020207.7(ERCC6L2):c.-15C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0943 in 1,584,238 control chromosomes in the GnomAD database, including 8,015 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.086 ( 753 hom., cov: 32)

Exomes 𝑓: 0.095 ( 7262 hom. )

Consequence

ERCC6L2
NM_020207.7 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.20

Publications

16 publications found

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 was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00238809).

BP6

Variant 9-95876024-C-T is Benign according to our data. Variant chr9-95876024-C-T is described in ClinVar as Benign. ClinVar VariationId is 1169826.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020207.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ERCC6L2	NM_020207.7	MANE Select	c.-15C>T	5_prime_UTR	Exon 1 of 19	NP_064592.3	Q5T890-1
ERCC6L2	NM_001375291.1		c.-15C>T	5_prime_UTR	Exon 1 of 19	NP_001362220.1
ERCC6L2	NM_001375292.1		c.-15C>T	5_prime_UTR	Exon 1 of 19	NP_001362221.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ERCC6L2	ENST00000653738.2	MANE Select	c.-15C>T	5_prime_UTR	Exon 1 of 19	ENSP00000499221.2	Q5T890-1
ERCC6L2	ENST00000288985.13	TSL:1	c.-15C>T	5_prime_UTR	Exon 1 of 14	ENSP00000288985.8	A0A5F9UKL4
ERCC6L2-AS1	ENST00000412446.6	TSL:1	n.26G>A	non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes

AF:

0.0860

AC:

13082

AN:

152174

Hom.:

750

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0343

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.135

Gnomad ASJ

AF:

0.0607

Gnomad EAS

AF:

0.165

Gnomad SAS

AF:

0.0923

Gnomad FIN

AF:

0.160

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0909

Gnomad OTH

AF:

0.0898

GnomAD2 exomes

AF:

0.115

AC:

22915

AN:

199718

AF XY:

0.110

show subpopulations

Gnomad AFR exome

AF:

0.0318

Gnomad AMR exome

AF:

0.194

Gnomad ASJ exome

AF:

0.0635

Gnomad EAS exome

AF:

0.165

Gnomad FIN exome

AF:

0.164

Gnomad NFE exome

AF:

0.0913

Gnomad OTH exome

AF:

0.106

GnomAD4 exome

AF:

0.0952

AC:

136360

AN:

1431946

Hom.:

7262

Cov.:

AF XY:

0.0949

AC XY:

67368

AN XY:

709878

show subpopulations

African (AFR)

AF:

0.0316

AC:

1033

AN:

32682

American (AMR)

AF:

0.188

AC:

7753

AN:

41134

Ashkenazi Jewish (ASJ)

AF:

0.0623

AC:

1589

AN:

25506

East Asian (EAS)

AF:

0.171

AC:

6418

AN:

37618

South Asian (SAS)

AF:

0.0934

AC:

7667

AN:

82110

European-Finnish (FIN)

AF:

0.160

AC:

7985

AN:

49808

Middle Eastern (MID)

AF:

0.0474

AC:

272

AN:

5740

European-Non Finnish (NFE)

AF:

0.0897

AC:

98511

AN:

1098138

Other (OTH)

AF:

0.0867

AC:

5132

AN:

59210

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

6566

13132

19697

26263

32829

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3698

7396

11094

14792

18490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0860

AC:

13092

AN:

152292

Hom.:

753

Cov.:

AF XY:

0.0905

AC XY:

6739

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.0342

AC:

1420

AN:

41576

American (AMR)

AF:

0.135

AC:

2070

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0607

AC:

210

AN:

3462

East Asian (EAS)

AF:

0.165

AC:

855

AN:

5184

South Asian (SAS)

AF:

0.0928

AC:

447

AN:

4818

European-Finnish (FIN)

AF:

0.160

AC:

1692

AN:

10606

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0909

AC:

6180

AN:

68016

Other (OTH)

AF:

0.0888

AC:

188

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

596

1192

1788

2384

2980

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

304

456

608

760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0881

Hom.:

851

Bravo

AF:

0.0836

TwinsUK

AF:

0.0863

AC:

320

ALSPAC

AF:

0.0903

AC:

348

ESP6500AA

AF:

0.0267

AC:

115

ESP6500EA

AF:

0.0851

AC:

721

ExAC

AF:

0.0956

AC:

11354

Asia WGS

AF:

0.118

AC:

409

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Pancytopenia-developmental delay syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.12

CADD

Benign

(source)

DANN

Uncertain

1.0

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.0076

LIST_S2

Benign

0.45

MetaRNN

Benign

0.0024

MetaSVM

Benign

-0.90

PhyloP100

1.2

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.24

REVEL

Benign

0.13

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.13

MPC

0.25

ClinPred

0.12

GERP RS

3.2

PromoterAI

0.055

Neutral

(source)

gMVP

0.20

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over