rs1547201

Positions:

• chr9-96054202-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000670016.1(ERCC6L2):​c.*1755+15075T>C variant causes a intron, NMD transcript 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, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.857

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERCC6L2	ENST00000670016.1	c.*1755+15075T>C		intron_variant, NMD_transcript_variant

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

Gnomad4 AFR AF: 0.499

Gnomad4 AMR AF: 0.440

Gnomad4 ASJ AF: 0.520

Gnomad4 EAS AF: 0.602

Gnomad4 SAS AF: 0.498

Gnomad4 FIN AF: 0.563

Gnomad4 NFE AF: 0.510

Gnomad4 OTH AF: 0.511

Alfa AF: 0.495 Hom.: 6222

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1547201; hg19: chr9-98816484;