9-95876014-G-T

Variant names:

• chr9-95876014-G-T
• rs761678165
• NM_020207.7:c.-25G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020207.7(ERCC6L2):​c.-25G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ERCC6L2 NM_020207.7 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00800
• Publications: 1 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-AS1 (HGNC:27858): (ERCC6L2 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020207.7. 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.-25G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 19	NP_064592.3	Q5T890-1
	ERCC6L2	NM_020207.7	MANE Select	c.-25G>T		5_prime_UTR	Exon 1 of 19	NP_064592.3	Q5T890-1
	ERCC6L2	NM_001375291.1		c.-25G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 19	NP_001362220.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERCC6L2	ENST00000653738.2	MANE Select	c.-25G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 19	ENSP00000499221.2	Q5T890-1
	ERCC6L2	ENST00000288985.13	TSL:1	c.-25G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 14	ENSP00000288985.8	A0A5F9UKL4
	ERCC6L2	ENST00000653738.2	MANE Select	c.-25G>T		5_prime_UTR	Exon 1 of 19	ENSP00000499221.2	Q5T890-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 190388 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1425202 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 705706

African (AFR) AF: 0.00 AC: 0 AN: 32466

American (AMR) AF: 0.00 AC: 0 AN: 40330

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25410

East Asian (EAS) AF: 0.00 AC: 0 AN: 37162

South Asian (SAS) AF: 0.00 AC: 0 AN: 81350

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49176

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5732

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1094632

Other (OTH) AF: 0.00 AC: 0 AN: 58944

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	4.5
DANN	Benign	0.80
PhyloP100		-0.0080
PromoterAI		-0.048	Neutral

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: rs761678165; hg19: chr9-98638296;