rs7867155

Positions:

• chr9-96065532-C-T

Variant summary

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

The ENST00000670016.1(ERCC6L2):​c.*1755+26405C>T variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,246 control chromosomes in the GnomAD database, including 1,412 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 0.13 (1412 hom., cov: 33)
• Consequence: ERCC6L2 ENST00000670016.1 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.634

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.188 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+26405C>T		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19082 AN: 152128 Hom.: 1408 Cov.: 33

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.0798

Gnomad ASJ AF: 0.0769

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0352

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.0967

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

GnomAD4 genome AF: 0.126 AC: 19120 AN: 152246 Hom.: 1412 Cov.: 33 AF XY: 0.123 AC XY: 9134 AN XY: 74442

Gnomad4 AFR AF: 0.191

Gnomad4 AMR AF: 0.0797

Gnomad4 ASJ AF: 0.0769

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0352

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.0957

Alfa AF: 0.113 Hom.: 544

Bravo AF: 0.126

Asia WGS AF: 0.0240 AC: 83 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.80
DANN	Benign	0.11

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7867155; hg19: chr9-98827814;