9-95876006-A-T

Variant names:

• chr9-95876006-A-T
• rs690528
• NM_020207.7:c.-33A>T

Variant summary

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

The NM_020207.7(ERCC6L2):​c.-33A>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. 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: -0.0600
• Publications: 19 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.-33A>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 19	NP_064592.3	Q5T890-1
	ERCC6L2	NM_020207.7	MANE Select	c.-33A>T		5_prime_UTR	Exon 1 of 19	NP_064592.3	Q5T890-1
	ERCC6L2	NM_001375291.1		c.-33A>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.-33A>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 19	ENSP00000499221.2	Q5T890-1
	ERCC6L2	ENST00000288985.13	TSL:1	c.-33A>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 14	ENSP00000288985.8	A0A5F9UKL4
	ERCC6L2	ENST00000653738.2	MANE Select	c.-33A>T		5_prime_UTR	Exon 1 of 19	ENSP00000499221.2	Q5T890-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1418974 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 702050

African (AFR) AF: 0.00 AC: 0 AN: 32310

American (AMR) AF: 0.00 AC: 0 AN: 39434

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25336

East Asian (EAS) AF: 0.00 AC: 0 AN: 36828

South Asian (SAS) AF: 0.00 AC: 0 AN: 80884

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48490

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5716

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1091252

Other (OTH) AF: 0.00 AC: 0 AN: 58724

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 5428

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.014	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	10
DANN	Benign	0.48
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0021	N
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.056	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-0.63	T
PhyloP100		-0.060
PROVEAN	Benign	-0.11	N
REVEL	Benign	0.24
Sift	Benign	0.43	T
Sift4G	Pathogenic	0.0	D
Vest4		0.26
MutPred		0.94		Gain of catalytic residue at M1 (P = 0.0558)
MVP		0.36
ClinPred		0.17	T
GERP RS		-3.7
PromoterAI		0.018	Neutral
gMVP		0.14
Mutation Taster		=188/12	polymorphism

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: rs690528; hg19: chr9-98638288;