dbSNP rs1482248980: ERCC6L2:c.-26C>T (chr9-95876013-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020207.7(ERCC6L2):c.-26C>T 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 0.00000211 in 1,424,380 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

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

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.526

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.054599136).

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.-26C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 19	NP_064592.3	Q5T890-1
ERCC6L2	NM_020207.7	MANE Select	c.-26C>T	5_prime_UTR	Exon 1 of 19	NP_064592.3	Q5T890-1
ERCC6L2	NM_001375291.1		c.-26C>T	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.-26C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 19	ENSP00000499221.2	Q5T890-1
ERCC6L2	ENST00000288985.13	TSL:1	c.-26C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 14	ENSP00000288985.8	A0A5F9UKL4
ERCC6L2	ENST00000653738.2	MANE Select	c.-26C>T	5_prime_UTR	Exon 1 of 19	ENSP00000499221.2	Q5T890-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000159

AC:

AN:

188894

AF XY:

0.0000292

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000343

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000407

GnomAD4 exome

AF:

0.00000211

AC:

AN:

1424380

Hom.:

Cov.:

AF XY:

0.00000425

AC XY:

AN XY:

705246

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32434

American (AMR)

AF:

0.0000746

AC:

AN:

40200

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25416

East Asian (EAS)

AF:

0.00

AC:

AN:

37138

South Asian (SAS)

AF:

0.00

AC:

AN:

81248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49108

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5732

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1094182

Other (OTH)

AF:

0.00

AC:

AN:

58922

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.0027

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Benign

0.91

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0017

LIST_S2

Benign

0.44

M_CAP

Benign

0.019

MetaRNN

Benign

0.055

MetaSVM

Benign

-0.70

PhyloP100

-0.53

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.89

REVEL

Benign

0.18

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.15

MutPred

0.13

Gain of stability (P = 0.0129)

MVP

0.21

MPC

0.23

ClinPred

0.12

GERP RS

-3.7

PromoterAI

-0.050

Neutral

(source)

gMVP

0.15

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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