rs7867155

Variant names:

• chr9-96065532-C-T
• rs7867155
• ENST00000670016.1:n.*1755+26405C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000670016.1(ERCC6L2):​n.*1755+26405C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,246 control chromosomes in the GnomAD database, including 1,412 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 0.13 (1412 hom., cov: 33)
• Consequence: ERCC6L2 ENST00000670016.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.634
• 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: G2P, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

ENSG00000237212 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000670016.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERCC6L2	ENST00000670016.1		n.*1755+26405C>T		intron	N/A	ENSP00000499338.1	A0A590UJA1
	ENSG00000237212	ENST00000652904.1		n.-236C>T		upstream_gene	N/A
	ENSG00000237212	ENST00000657490.1		n.-208C>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19082 AN: 152128 Hom.: 1408 Cov.: 33

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.0798

Gnomad ASJ AF: 0.0769

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0352

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.0967

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

GnomAD4 genome AF: 0.126 AC: 19120 AN: 152246 Hom.: 1412 Cov.: 33 AF XY: 0.123 AC XY: 9134 AN XY: 74442

African (AFR) AF: 0.191 AC: 7935 AN: 41538

American (AMR) AF: 0.0797 AC: 1220 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0769 AC: 267 AN: 3472

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5184

South Asian (SAS) AF: 0.0352 AC: 170 AN: 4828

European-Finnish (FIN) AF: 0.141 AC: 1495 AN: 10602

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7684 AN: 68004

Other (OTH) AF: 0.0957 AC: 202 AN: 2110

Alfa AF: 0.112 Hom.: 781

Bravo AF: 0.126

Asia WGS AF: 0.0240 AC: 83 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.80
DANN	Benign	0.11
PhyloP100		-0.63

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs7867155;

hg19: chr9-98827814;