Genetic Variant ERCC6L2:c.-8C>A (chr9-95876031-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020207.7(ERCC6L2):c.-8C>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000209 in 1,436,000 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ERCC6L2
NM_020207.7 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.100

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10260165).

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.-8C>A	5_prime_UTR_premature_start_codon_gain	Exon 1 of 19	NP_064592.3	Q5T890-1
ERCC6L2	NM_020207.7	MANE Select	c.-8C>A	5_prime_UTR	Exon 1 of 19	NP_064592.3	Q5T890-1
ERCC6L2	NM_001375291.1		c.-8C>A	5_prime_UTR_premature_start_codon_gain	Exon 1 of 19	NP_001362220.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ERCC6L2	ENST00000653738.2	MANE Select	c.-8C>A	5_prime_UTR_premature_start_codon_gain	Exon 1 of 19	ENSP00000499221.2	Q5T890-1
ERCC6L2	ENST00000288985.13	TSL:1	c.-8C>A	5_prime_UTR_premature_start_codon_gain	Exon 1 of 14	ENSP00000288985.8	A0A5F9UKL4
ERCC6L2	ENST00000653738.2	MANE Select	c.-8C>A	5_prime_UTR	Exon 1 of 19	ENSP00000499221.2	Q5T890-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000209

AC:

AN:

1436000

Hom.:

Cov.:

AF XY:

0.00000281

AC XY:

AN XY:

712230

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32794

American (AMR)

AF:

0.00

AC:

AN:

41762

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25556

East Asian (EAS)

AF:

0.00

AC:

AN:

37882

South Asian (SAS)

AF:

0.00

AC:

AN:

82412

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50212

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.00000273

AC:

AN:

1100286

Other (OTH)

AF:

0.00

AC:

AN:

59348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Uncertain

0.097

BayesDel_noAF

Benign

-0.10

CADD

Benign

(source)

DANN

Uncertain

0.99

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0043

LIST_S2

Benign

0.29

M_CAP

Benign

0.062

MetaRNN

Benign

0.10

MetaSVM

Benign

-0.59

PhyloP100

-0.10

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.21

REVEL

Benign

0.17

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.038

Vest4

0.31

MutPred

0.10

Loss of glycosylation at P9 (P = 0.0152)

MVP

0.31

MPC

0.45

ClinPred

0.30

GERP RS

-1.7

PromoterAI

0.0073

Neutral

(source)

gMVP

0.20

Mutation Taster

=99/1

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over