rs78293324

Variant names:

• chr9-95876031-C-G
• rs78293324
• NM_020207.7:c.-8C>G

Your query was ambiguous. Multiple possible variants found:

• chr9-95876031-C-G
• chr9-95876031-C-A
• chr9-95876031-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_020207.7(ERCC6L2):​c.-8C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00233 in 1,588,360 control chromosomes in the GnomAD database, including 68 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0031 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (63 hom.)
• Consequence: ERCC6L2 NM_020207.7 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.100
• Publications: 3 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0030474067).
• BP6: Variant 9-95876031-C-G is Benign according to our data. Variant chr9-95876031-C-G is described in ClinVar as Benign. ClinVar VariationId is 732858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00308 (469/152370) while in subpopulation EAS AF = 0.0353 (183/5186). AF 95% confidence interval is 0.0311. There are 5 homozygotes in GnomAd4. There are 324 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

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.-8C>G		5_prime_UTR	Exon 1 of 19	NP_064592.3	Q5T890-1
	ERCC6L2	NM_001375291.1		c.-8C>G		5_prime_UTR	Exon 1 of 19	NP_001362220.1
	ERCC6L2	NM_001375292.1		c.-8C>G		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.-8C>G		5_prime_UTR	Exon 1 of 19	ENSP00000499221.2	Q5T890-1
	ERCC6L2	ENST00000288985.13	TSL:1	c.-8C>G		5_prime_UTR	Exon 1 of 14	ENSP00000288985.8	A0A5F9UKL4
	ERCC6L2-AS1	ENST00000412446.6	TSL:1	n.19G>C		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.00308 AC: 469 AN: 152252 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0352

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.0216

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000705

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00410 AC: 840 AN: 204736 AF XY: 0.00390

Gnomad AFR exome AF: 0.0000877

Gnomad AMR exome AF: 0.0000324

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0285

Gnomad FIN exome AF: 0.0183

Gnomad NFE exome AF: 0.000572

Gnomad OTH exome AF: 0.00154

GnomAD4 exome AF: 0.00225 AC: 3233 AN: 1435990 Hom.: 63 Cov.: 32 AF XY: 0.00220 AC XY: 1567 AN XY: 712224

African (AFR) AF: 0.0000305 AC: 1 AN: 32794

American (AMR) AF: 0.0000239 AC: 1 AN: 41762

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25556

East Asian (EAS) AF: 0.0517 AC: 1959 AN: 37878

South Asian (SAS) AF: 0.00115 AC: 95 AN: 82412

European-Finnish (FIN) AF: 0.0180 AC: 904 AN: 50206

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5748

European-Non Finnish (NFE) AF: 0.000157 AC: 173 AN: 1100286

Other (OTH) AF: 0.00167 AC: 99 AN: 59348

GnomAD4 genome AF: 0.00308 AC: 469 AN: 152370 Hom.: 5 Cov.: 32 AF XY: 0.00435 AC XY: 324 AN XY: 74504

African (AFR) AF: 0.00 AC: 0 AN: 41592

American (AMR) AF: 0.0000653 AC: 1 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.0353 AC: 183 AN: 5186

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4824

European-Finnish (FIN) AF: 0.0216 AC: 230 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000705 AC: 48 AN: 68038

Other (OTH) AF: 0.00189 AC: 4 AN: 2116

Alfa AF: 0.00122 Hom.: 0

Bravo AF: 0.00143

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000118 AC: 1

ExAC AF: 0.00343 AC: 411

Asia WGS AF: 0.0100 AC: 35 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.11
CADD	Benign	12
DANN	Uncertain	0.99
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0036	N
LIST_S2	Benign	0.34	T
MetaRNN	Benign	0.0030	T
MetaSVM	Benign	-0.81	T
PhyloP100		-0.10
PrimateAI	Benign	0.44	T
PROVEAN	Benign	0.28	N
REVEL	Benign	0.17
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.049	D
Vest4		0.27
MVP		0.29
MPC		0.34
ClinPred		0.029	T
GERP RS		-1.7
PromoterAI		0.0045	Neutral
gMVP		0.19
Mutation Taster		=99/1	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: rs78293324; hg19: chr9-98638313; COSMIC: COSV56631747; COSMIC: COSV56631747;