9-95966906-C-G

Variant names:

• chr9-95966906-C-G
• rs589362
• ENST00000288985.13:c.*186C>G

Variant summary

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

The NM_001010895.4(ERCC6L2):​c.*186C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 401,512 control chromosomes in the GnomAD database, including 18,343 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 0.27 (5970 hom., cov: 32)
  • Exomes 𝑓: 0.31 (12373 hom.)
• Consequence: ERCC6L2 NM_001010895.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.944
• Publications: 6 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: Orphanet, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010895.4. 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
	ERCC6L2	NM_020207.7	MANE Select	c.2100+192C>G		intron	N/A	NP_064592.3	Q5T890-1
	ERCC6L2	NM_001010895.4		c.*186C>G		3_prime_UTR	Exon 14 of 14	NP_001010895.2	Q5T890-2
	ERCC6L2	NM_001375291.1		c.2100+192C>G		intron	N/A	NP_001362220.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERCC6L2	ENST00000288985.13	TSL:1	c.*186C>G		3_prime_UTR	Exon 14 of 14	ENSP00000288985.8	A0A5F9UKL4
	ERCC6L2	ENST00000653738.2	MANE Select	c.2100+192C>G		intron	N/A	ENSP00000499221.2	Q5T890-1
	ERCC6L2	ENST00000466840.5	TSL:1	n.3332C>G		non_coding_transcript_exon	Exon 15 of 15

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40714 AN: 151894 Hom.: 5972 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.278

GnomAD4 exome AF: 0.310 AC: 77413 AN: 249500 Hom.: 12373 Cov.: 4 AF XY: 0.311 AC XY: 39732 AN XY: 127726

African (AFR) AF: 0.148 AC: 1097 AN: 7394

American (AMR) AF: 0.315 AC: 2535 AN: 8036

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 3371 AN: 8718

East Asian (EAS) AF: 0.376 AC: 8109 AN: 21574

South Asian (SAS) AF: 0.266 AC: 1499 AN: 5642

European-Finnish (FIN) AF: 0.275 AC: 4921 AN: 17868

Middle Eastern (MID) AF: 0.267 AC: 329 AN: 1230

European-Non Finnish (NFE) AF: 0.312 AC: 50894 AN: 163352

Other (OTH) AF: 0.297 AC: 4658 AN: 15686

GnomAD4 genome AF: 0.268 AC: 40720 AN: 152012 Hom.: 5970 Cov.: 32 AF XY: 0.271 AC XY: 20099 AN XY: 74284

African (AFR) AF: 0.145 AC: 5999 AN: 41496

American (AMR) AF: 0.310 AC: 4725 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.375 AC: 1298 AN: 3462

East Asian (EAS) AF: 0.398 AC: 2055 AN: 5160

South Asian (SAS) AF: 0.270 AC: 1304 AN: 4822

European-Finnish (FIN) AF: 0.279 AC: 2944 AN: 10552

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.314 AC: 21342 AN: 67970

Other (OTH) AF: 0.275 AC: 578 AN: 2100

Alfa AF: 0.286 Hom.: 799

Bravo AF: 0.264

Asia WGS AF: 0.278 AC: 964 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.35
DANN	Benign	0.44
PhyloP100		-0.94
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: rs589362; hg19: chr9-98729188;