9-96013177-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020207.7(ERCC6L2):​c.4627G>T​(p.Ala1543Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000825 in 1,212,690 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 6/6 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1543T) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 8.2e-7 (0 hom.)
• Consequence: ERCC6L2 NM_020207.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.125
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.011).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERCC6L2	NM_020207.7	c.4627G>T	p.Ala1543Ser	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>T	p.Ala1543Ser	missense_variant	Exon 19 of 19		NM_020207.7	ENSP00000499221.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.25e-7 AC: 1 AN: 1212690 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 601206

African (AFR) AF: 0.00 AC: 0 AN: 25902

American (AMR) AF: 0.00 AC: 0 AN: 36442

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16750

East Asian (EAS) AF: 0.00 AC: 0 AN: 16788

South Asian (SAS) AF: 0.00 AC: 0 AN: 82984

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32490

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4452

European-Non Finnish (NFE) AF: 0.00000105 AC: 1 AN: 953066

Other (OTH) AF: 0.00 AC: 0 AN: 43816

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.10
DANN	Benign	0.71
PhyloP100		0.13
Mutation Taster		=100/0	polymorphism

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;