rs549498051

Variant names:

• chr7-5997426-GAAA-G
• rs60794673
• NM_000535.7:c.706-6_706-4delTTT

Your query was ambiguous. Multiple possible variants found:

• chr7-5997426-GAAA-G
• chr7-5997426-G-GAAAAAAA
• chr7-5997426-GAA-G
• chr7-5997426-G-GAAAAAAAAAAAAAAAA
• chr7-5997426-GAAAA-G
• chr7-5997426-GA-G
• chr7-5997426-G-GA
• chr7-5997426-G-GAA
• chr7-5997426-G-GAAA

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS1

The NM_000535.7(PMS2):​c.706-6_706-4delTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00389 in 1,092,160 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000068 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0044 (0 hom.)
• Consequence: PMS2 NM_000535.7 splice_region, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.187

Genes affected

PMS2 (HGNC:9122): (PMS1 homolog 2, mismatch repair system component) The protein encoded by this gene is a key component of the mismatch repair system that functions to correct DNA mismatches and small insertions and deletions that can occur during DNA replication and homologous recombination. This protein forms heterodimers with the gene product of the mutL homolog 1 (MLH1) gene to form the MutL-alpha heterodimer. The MutL-alpha heterodimer possesses an endonucleolytic activity that is activated following recognition of mismatches and insertion/deletion loops by the MutS-alpha and MutS-beta heterodimers, and is necessary for removal of the mismatched DNA. There is a DQHA(X)2E(X)4E motif found at the C-terminus of the protein encoded by this gene that forms part of the active site of the nuclease. Mutations in this gene have been associated with hereditary nonpolyposis colorectal cancer (HNPCC; also known as Lynch syndrome) and Turcot syndrome. [provided by RefSeq, Apr 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP6: Variant 7-5997426-GAAA-G is Benign according to our data. Variant chr7-5997426-GAAA-G is described in ClinVar as [Likely_benign]. Clinvar id is 286329.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-5997426-GAAA-G is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.00442 (4243/958902) while in subpopulation AFR AF= 0.00611 (135/22086). AF 95% confidence interval is 0.00527. There are 0 homozygotes in gnomad4_exome. There are 2123 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PMS2	NM_000535.7	c.706-6_706-4delTTT		splice_region_variant, intron_variant	Intron 6 of 14	ENST00000265849.12	NP_000526.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PMS2	ENST00000265849.12	c.706-6_706-4delTTT		splice_region_variant, intron_variant	Intron 6 of 14	1	NM_000535.7	ENSP00000265849.7

Frequencies

GnomAD3 genomes AF: 0.0000676 AC: 9 AN: 133216 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000287

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000760

Gnomad ASJ AF: 0.000310

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000275

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000638

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00442 AC: 4243 AN: 958902 Hom.: 0 AF XY: 0.00432 AC XY: 2123 AN XY: 491112

Gnomad4 AFR exome AF: 0.00611

Gnomad4 AMR exome AF: 0.00456

Gnomad4 ASJ exome AF: 0.00304

Gnomad4 EAS exome AF: 0.00550

Gnomad4 SAS exome AF: 0.00422

Gnomad4 FIN exome AF: 0.00171

Gnomad4 NFE exome AF: 0.00459

Gnomad4 OTH exome AF: 0.00407

GnomAD4 genome AF: 0.0000675 AC: 9 AN: 133258 Hom.: 0 Cov.: 0 AF XY: 0.0000784 AC XY: 5 AN XY: 63796

Gnomad4 AFR AF: 0.0000286

Gnomad4 AMR AF: 0.0000759

Gnomad4 ASJ AF: 0.000310

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000275

Gnomad4 NFE AF: 0.0000638

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 25, 2016

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hereditary cancer-predisposing syndrome Benign:2

Jan 04, 2024

Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 06, 2017

Color Diagnostics, LLC DBA Color Health

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breast and/or ovarian cancer Benign:1

May 24, 2023

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Jul 01, 2019

Quest Diagnostics Nichols Institute San Juan Capistrano

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hereditary nonpolyposis colorectal neoplasms Benign:1

Jun 07, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Malignant tumor of breast Benign:1

-

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Gnom AD population frequency 44% -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs60794673; hg19: chr7-6037057;