9-95929529-A-G

Position:

• chr9-95929529-A-G

Variant summary

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

The NM_020207.7(ERCC6L2):​c.1751+665A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 152,116 control chromosomes in the GnomAD database, including 5,891 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 0.26 (5891 hom., cov: 32)
• Consequence: ERCC6L2 NM_020207.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0930

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERCC6L2	NM_020207.7	c.1751+665A>G		intron_variant		ENST00000653738.2	NP_064592.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERCC6L2	ENST00000653738.2	c.1751+665A>G		intron_variant			NM_020207.7	ENSP00000499221.2

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40117 AN: 151998 Hom.: 5893 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.278

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

GnomAD4 genome AF: 0.264 AC: 40121 AN: 152116 Hom.: 5891 Cov.: 32 AF XY: 0.267 AC XY: 19846 AN XY: 74398

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.308

Gnomad4 ASJ AF: 0.374

Gnomad4 EAS AF: 0.399

Gnomad4 SAS AF: 0.271

Gnomad4 FIN AF: 0.279

Gnomad4 NFE AF: 0.314

Gnomad4 OTH AF: 0.275

Alfa AF: 0.292 Hom.: 824

Bravo AF: 0.260

Asia WGS AF: 0.278 AC: 965 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.24
DANN	Benign	0.86

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

LitVar

Other links and lift over

dbSNP: rs10512245; hg19: chr9-98691811;