ENST00000670016.1:n.*1755+15075T>C

Variant names:

• chr9-96054202-T-C
• rs1547201
• ENST00000670016.1:n.*1755+15075T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000670016.1(ERCC6L2):​n.*1755+15075T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 152,198 control chromosomes in the GnomAD database, including 19,641 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 0.51 (19641 hom., cov: 33)
• Consequence: ERCC6L2 ENST00000670016.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.857
• Publications: 6 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERCC6L2	ENST00000670016.1	n.*1755+15075T>C		intron_variant	Intron 20 of 20			ENSP00000499338.1

Frequencies

GnomAD3 genomes AF: 0.507 AC: 77055 AN: 152080 Hom.: 19637 Cov.: 33

Gnomad AFR AF: 0.500

Gnomad AMI AF: 0.550

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.602

Gnomad SAS AF: 0.497

Gnomad FIN AF: 0.563

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.510

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.507 AC: 77089 AN: 152198 Hom.: 19641 Cov.: 33 AF XY: 0.510 AC XY: 37942 AN XY: 74384

African (AFR) AF: 0.499 AC: 20735 AN: 41542

American (AMR) AF: 0.440 AC: 6725 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.520 AC: 1804 AN: 3470

East Asian (EAS) AF: 0.602 AC: 3103 AN: 5156

South Asian (SAS) AF: 0.498 AC: 2403 AN: 4826

European-Finnish (FIN) AF: 0.563 AC: 5960 AN: 10590

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.510 AC: 34652 AN: 68000

Other (OTH) AF: 0.511 AC: 1082 AN: 2116

Alfa AF: 0.500 Hom.: 14196

Bravo AF: 0.492

Asia WGS AF: 0.520 AC: 1804 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.20
DANN	Benign	0.56
PhyloP100		-0.86

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1547201; hg19: chr9-98816484;