rs1827238722

Variant names:

• chr9-95876026-TC-T
• rs1827238722
• NM_020207.7:c.-8delC

Your query was ambiguous. Multiple possible variants found:

• chr9-95876026-TC-T
• chr9-95876026-TC-TCC

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP5_Moderate

The NM_020207.7(ERCC6L2):​c.-8delC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000209 in 1,433,042 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ERCC6L2 NM_020207.7 5_prime_UTR
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: -0.0900
• 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-AS1 (HGNC:27858): (ERCC6L2 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 9-95876026-TC-T is Pathogenic according to our data. Variant chr9-95876026-TC-T is described in ClinVar as Pathogenic. ClinVar VariationId is 3692630.Status of the report is criteria_provided_single_submitter, 1 stars.

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.-8delC		5_prime_UTR	Exon 1 of 19	NP_064592.3	Q5T890-1
	ERCC6L2	NM_001375291.1		c.-8delC		5_prime_UTR	Exon 1 of 19	NP_001362220.1
	ERCC6L2	NM_001375292.1		c.-8delC		5_prime_UTR	Exon 1 of 19	NP_001362221.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERCC6L2	ENST00000653738.2	MANE Select	c.-8delC		5_prime_UTR	Exon 1 of 19	ENSP00000499221.2	Q5T890-1
	ERCC6L2	ENST00000288985.13	TSL:1	c.-8delC		5_prime_UTR	Exon 1 of 14	ENSP00000288985.8	A0A5F9UKL4
	ERCC6L2-AS1	ENST00000412446.6	TSL:1	n.23delG		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000209 AC: 3 AN: 1433042 Hom.: 0 Cov.: 31 AF XY: 0.00000141 AC XY: 1 AN XY: 710494

African (AFR) AF: 0.00 AC: 0 AN: 32700

American (AMR) AF: 0.00 AC: 0 AN: 41440

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25528

East Asian (EAS) AF: 0.00 AC: 0 AN: 37746

South Asian (SAS) AF: 0.00 AC: 0 AN: 82184

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49804

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.00000182 AC: 2 AN: 1098652

Other (OTH) AF: 0.0000169 AC: 1 AN: 59242

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.090

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: rs1827238722; hg19: chr9-98638308;