rs747115098

chr8-31120426-TA-Tchr8-31120426-TA-TAA

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_000553.6(WRN):c.2630+10del variant causes a splice donor region, intron change. The variant allele was found at a frequency of 0.00000823 in 1,458,640 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: WRN NM_000553.6 splice_donor_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.67

Genes affected

WRN (HGNC:12791): (WRN RecQ like helicase) This gene encodes a member of the RecQ subfamily of DNA helicase proteins. The encoded nuclear protein is important in the maintenance of genome stability and plays a role in DNA repair, replication, transcription and telomere maintenance. This protein contains a N-terminal 3' to 5' exonuclease domain, an ATP-dependent helicase domain and RQC (RecQ helicase conserved region) domain in its central region, and a C-terminal HRDC (helicase RNase D C-terminal) domain and nuclear localization signal. Defects in this gene are the cause of Werner syndrome, an autosomal recessive disorder characterized by accelerated aging and an elevated risk for certain cancers. [provided by RefSeq, Aug 2017]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 8-31120426-TA-T is Benign according to our data. Variant chr8-31120426-TA-T is described in ClinVar as [Likely_benign]. Clinvar id is 1117147.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WRN	NM_000553.6	c.2630+10del		splice_donor_region_variant, intron_variant		ENST00000298139.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WRN	ENST00000298139.7	c.2630+10del		splice_donor_region_variant, intron_variant		1	NM_000553.6	P1
WRN	ENST00000521620.5	n.1263+10del		splice_donor_region_variant, intron_variant, non_coding_transcript_variant		1
WRN	ENST00000650667.1	c.*2244+10del		splice_donor_region_variant, intron_variant, NMD_transcript_variant
WRN	ENST00000520169.1	n.469+10del		splice_donor_region_variant, intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000823 AC: 12 AN: 1458640 Hom.: 0 Cov.: 32 AF XY: 0.0000124 AC XY: 9 AN XY: 725598

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000177

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.0000332

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Werner syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Sep 18, 2023

- -

Computational scores

Source: dbNSFP v4.3

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: rs747115098; hg19: chr8-30977942;