9-95929529-A-G

Variant names:

• chr9-95929529-A-G
• rs10512245
• NM_020207.7:c.1751+665A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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 -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 rank	MANE	Protein	UniProt
ERCC6L2	NM_020207.7	c.1751+665A>G		intron_variant	Intron 11 of 18	ENST00000653738.2	NP_064592.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERCC6L2	ENST00000653738.2	c.1751+665A>G		intron_variant	Intron 11 of 18		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

African (AFR) AF: 0.130 AC: 5410 AN: 41498

American (AMR) AF: 0.308 AC: 4706 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 1300 AN: 3472

East Asian (EAS) AF: 0.399 AC: 2065 AN: 5172

South Asian (SAS) AF: 0.271 AC: 1307 AN: 4828

European-Finnish (FIN) AF: 0.279 AC: 2952 AN: 10574

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.314 AC: 21326 AN: 67982

Other (OTH) AF: 0.275 AC: 580 AN: 2112

Alfa AF: 0.286 Hom.: 832

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
PhyloP100		-0.093
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10512245; hg19: chr9-98691811;