rs589362

Positions:

• chr9-95966906-C-G
• chr9-95966906-C-T

Variant summary

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

The NM_020207.7(ERCC6L2):​c.2100+192C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 401,512 control chromosomes in the GnomAD database, including 18,343 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 0.27 (5970 hom., cov: 32)
  • Exomes 𝑓: 0.31 (12373 hom.)
• Consequence: ERCC6L2 NM_020207.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.944

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERCC6L2	NM_020207.7	c.2100+192C>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.2100+192C>G		intron_variant			NM_020207.7	ENSP00000499221	P2

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40714 AN: 151894 Hom.: 5972 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.278

GnomAD4 exome AF: 0.310 AC: 77413 AN: 249500 Hom.: 12373 Cov.: 4 AF XY: 0.311 AC XY: 39732 AN XY: 127726

Gnomad4 AFR exome AF: 0.148

Gnomad4 AMR exome AF: 0.315

Gnomad4 ASJ exome AF: 0.387

Gnomad4 EAS exome AF: 0.376

Gnomad4 SAS exome AF: 0.266

Gnomad4 FIN exome AF: 0.275

Gnomad4 NFE exome AF: 0.312

Gnomad4 OTH exome AF: 0.297

GnomAD4 genome AF: 0.268 AC: 40720 AN: 152012 Hom.: 5970 Cov.: 32 AF XY: 0.271 AC XY: 20099 AN XY: 74284

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.310

Gnomad4 ASJ AF: 0.375

Gnomad4 EAS AF: 0.398

Gnomad4 SAS AF: 0.270

Gnomad4 FIN AF: 0.279

Gnomad4 NFE AF: 0.314

Gnomad4 OTH AF: 0.275

Alfa AF: 0.286 Hom.: 799

Bravo AF: 0.264

Asia WGS AF: 0.278 AC: 964 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.35
DANN	Benign	0.44

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: rs589362; hg19: chr9-98729188;