rs10512243

Variant names:

• chr9-96013177-G-A
• rs10512243
• NM_020207.7:c.4627G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-96013177-G-A
• chr9-96013177-G-T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong 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. 6/6 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, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.125
• Publications: 8 publications found

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 Gene-Disease associations (from GenCC):

• pancytopenia-developmental delay syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, G2P

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.045).
• BP6: Variant 9-96013177-G-A is Benign according to our data. Variant chr9-96013177-G-A is described in ClinVar as Benign. ClinVar VariationId is 1167166.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
ERCC6L2	NM_020207.7	c.4627G>A	p.Ala1543Thr	missense_variant	Exon 19 of 19	ENST00000653738.2	NP_064592.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERCC6L2	ENST00000653738.2	c.4627G>A	p.Ala1543Thr	missense_variant	Exon 19 of 19		NM_020207.7	ENSP00000499221.2

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

GnomAD2 exomes AF: 0.104 AC: 25457 AN: 245288 AF XY: 0.0992

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 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

African (AFR) AF: 0.0643 AC: 1664 AN: 25896

American (AMR) AF: 0.197 AC: 7162 AN: 36424

Ashkenazi Jewish (ASJ) AF: 0.0607 AC: 1016 AN: 16750

East Asian (EAS) AF: 0.0583 AC: 978 AN: 16786

South Asian (SAS) AF: 0.0886 AC: 7355 AN: 82974

European-Finnish (FIN) AF: 0.124 AC: 4038 AN: 32490

Middle Eastern (MID) AF: 0.0369 AC: 164 AN: 4450

European-Non Finnish (NFE) AF: 0.0893 AC: 85066 AN: 952750

Other (OTH) AF: 0.0804 AC: 3521 AN: 43808

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

African (AFR) AF: 0.0685 AC: 2843 AN: 41522

American (AMR) AF: 0.135 AC: 2068 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0585 AC: 203 AN: 3468

East Asian (EAS) AF: 0.0519 AC: 269 AN: 5186

South Asian (SAS) AF: 0.0885 AC: 427 AN: 4826

European-Finnish (FIN) AF: 0.122 AC: 1287 AN: 10566

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0890 AC: 6054 AN: 67986

Other (OTH) AF: 0.0906 AC: 191 AN: 2108

Alfa AF: 0.0868 Hom.: 1192

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:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Pancytopenia-developmental delay syndrome Benign:1

Nov 15, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.26
DANN	Benign	0.18
PhyloP100		0.13
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs10512243; hg19: chr9-98775459;