rs10512243

chr9-96013177-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_020207.7(ERCC6L2):c.4627G>A(p.Ala1543Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0911 in 1,364,476 control chromosomes in the GnomAD database, including 6,279 homozygotes. In-silico tool predicts a benign outcome for this variant. 4/4 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.088 (668 hom., cov: 33)
  • Exomes 𝑓: 0.092 (5611 hom.)
• Consequence: ERCC6L2 NM_020207.7 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.125

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 9-96013177-G-A is Benign according to our data. Variant chr9-96013177-G-A is described in ClinVar as [Benign]. Clinvar id is 1167166.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERCC6L2	NM_020207.7	c.4627G>A	p.Ala1543Thr	missense_variant	19/19	ENST00000653738.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERCC6L2	ENST00000653738.2	c.4627G>A	p.Ala1543Thr	missense_variant	19/19		NM_020207.7	P2

Frequencies

GnomAD3 genomes AF: 0.0879 AC: 13361 AN: 152030 Hom.: 666 Cov.: 33

Gnomad AFR AF: 0.0686

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.0585

Gnomad EAS AF: 0.0519

Gnomad SAS AF: 0.0884

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0891

Gnomad OTH AF: 0.0906

GnomAD3 exomes AF: 0.104 AC: 25457 AN: 245288 Hom.: 1613 AF XY: 0.0992 AC XY: 13212 AN XY: 133180

Gnomad AFR exome AF: 0.0697

Gnomad AMR exome AF: 0.198

Gnomad ASJ exome AF: 0.0602

Gnomad EAS exome AF: 0.0565

Gnomad SAS exome AF: 0.0898

Gnomad FIN exome AF: 0.123

Gnomad NFE exome AF: 0.0917

Gnomad OTH exome AF: 0.101

GnomAD4 exome AF: 0.0915 AC: 110964 AN: 1212328 Hom.: 5611 Cov.: 32 AF XY: 0.0909 AC XY: 54637 AN XY: 601066

Gnomad4 AFR exome AF: 0.0643

Gnomad4 AMR exome AF: 0.197

Gnomad4 ASJ exome AF: 0.0607

Gnomad4 EAS exome AF: 0.0583

Gnomad4 SAS exome AF: 0.0886

Gnomad4 FIN exome AF: 0.124

Gnomad4 NFE exome AF: 0.0893

Gnomad4 OTH exome AF: 0.0804

GnomAD4 genome AF: 0.0879 AC: 13374 AN: 152148 Hom.: 668 Cov.: 33 AF XY: 0.0899 AC XY: 6689 AN XY: 74364

Gnomad4 AFR AF: 0.0685

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.0585

Gnomad4 EAS AF: 0.0519

Gnomad4 SAS AF: 0.0885

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.0890

Gnomad4 OTH AF: 0.0906

Alfa AF: 0.0861 Hom.: 966

Bravo AF: 0.0892

Asia WGS AF: 0.0720 AC: 249 AN: 3478

EpiCase AF: 0.0825

EpiControl AF: 0.0856

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.26
Dann	Benign	0.18

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10512243; hg19: chr9-98775459;