9-95876006-A-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERCC6L2	NM_020207.7	c.-33A>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 19	ENST00000653738.2	NP_064592.3
ERCC6L2	NM_020207.7	c.-33A>T		5_prime_UTR_variant	Exon 1 of 19	ENST00000653738.2	NP_064592.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERCC6L2	ENST00000653738	c.-33A>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 19		NM_020207.7	ENSP00000499221.2
ERCC6L2	ENST00000653738	c.-33A>T		5_prime_UTR_variant	Exon 1 of 19		NM_020207.7	ENSP00000499221.2

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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
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
gMVP		0.14

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

Publications

LitVar

Other links and lift over

dbSNP: rs690528; hg19: chr9-98638288;