Genetic Variant ERCC6L2:n.3332C>G (chr9-95966906-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000466840.5(ERCC6L2):n.3332C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 401,512 control chromosomes in the GnomAD database, including 18,343 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 0.27 ( 5970 hom., cov: 32)

Exomes 𝑓: 0.31 ( 12373 hom. )

Consequence

ERCC6L2
ENST00000466840.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.944

Publications

6 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 Gene-Disease associations (from GenCC):

pancytopenia-developmental delay syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, G2P

ERCC6L2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERCC6L2	NM_020207.7 link	c.2100+192C>G		intron_variant	Intron 14 of 18	ENST00000653738.2	NP_064592.3	Q5T890

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERCC6L2	ENST00000653738.2 link	c.2100+192C>G		intron_variant	Intron 14 of 18		NM_020207.7	ENSP00000499221.2		A0A590UJ07

Frequencies

GnomAD3 genomes

AF:

0.268

AC:

40714

AN:

151894

Hom.:

5972

Cov.:

show subpopulations

Gnomad AFR

AF:

0.145

Gnomad AMI

AF:

0.432

Gnomad AMR

AF:

0.310

Gnomad ASJ

AF:

0.375

Gnomad EAS

AF:

0.399

Gnomad SAS

AF:

0.269

Gnomad FIN

AF:

0.279

Gnomad MID

AF:

0.288

Gnomad NFE

AF:

0.314

Gnomad OTH

AF:

0.278

GnomAD4 exome

AF:

0.310

AC:

77413

AN:

249500

Hom.:

12373

Cov.:

AF XY:

0.311

AC XY:

39732

AN XY:

127726

show subpopulations

African (AFR)

AF:

0.148

AC:

1097

AN:

7394

American (AMR)

AF:

0.315

AC:

2535

AN:

8036

Ashkenazi Jewish (ASJ)

AF:

0.387

AC:

3371

AN:

8718

East Asian (EAS)

AF:

0.376

AC:

8109

AN:

21574

South Asian (SAS)

AF:

0.266

AC:

1499

AN:

5642

European-Finnish (FIN)

AF:

0.275

AC:

4921

AN:

17868

Middle Eastern (MID)

AF:

0.267

AC:

329

AN:

1230

European-Non Finnish (NFE)

AF:

0.312

AC:

50894

AN:

163352

Other (OTH)

AF:

0.297

AC:

4658

AN:

15686

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

2470

4939

7409

9878

12348

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

430

860

1290

1720

2150

<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:

0.268

AC:

40720

AN:

152012

Hom.:

5970

Cov.:

AF XY:

0.271

AC XY:

20099

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.145

AC:

5999

AN:

41496

American (AMR)

AF:

0.310

AC:

4725

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.375

AC:

1298

AN:

3462

East Asian (EAS)

AF:

0.398

AC:

2055

AN:

5160

South Asian (SAS)

AF:

0.270

AC:

1304

AN:

4822

European-Finnish (FIN)

AF:

0.279

AC:

2944

AN:

10552

Middle Eastern (MID)

AF:

0.282

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.314

AC:

21342

AN:

67970

Other (OTH)

AF:

0.275

AC:

578

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1475

2949

4424

5898

7373

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

438

876

1314

1752

2190

<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:

0.286

Hom.:

799

Bravo

AF:

0.264

Asia WGS

AF:

0.278

AC:

964

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.35

(source)

DANN

Benign

0.44

PhyloP100

-0.94

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over