2-189805813-T-TA

Position:

• chr2-189805813-T-TA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000534.5(PMS1):​c.418+70dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 1,353,866 control chromosomes in the GnomAD database, including 9,570 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (3958 hom., cov: 25)
  • Exomes 𝑓: 0.21 (5612 hom.)
• Consequence: PMS1 NM_000534.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.609

Genes affected

PMS1 (HGNC:9121): (PMS1 homolog 1, mismatch repair system component) This gene encodes a protein belonging to the DNA mismatch repair mutL/hexB family. This protein is thought to be involved in the repair of DNA mismatches, and it can form heterodimers with MLH1, a known DNA mismatch repair protein. Mutations in this gene cause hereditary nonpolyposis colorectal cancer type 3 (HNPCC3) either alone or in combination with mutations in other genes involved in the HNPCC phenotype, which is also known as Lynch syndrome. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 2-189805813-T-TA is Benign according to our data. Variant chr2-189805813-T-TA is described in ClinVar as [Benign]. Clinvar id is 1228750.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PMS1	NM_000534.5	c.418+70dup		intron_variant		ENST00000441310.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PMS1	ENST00000441310.7	c.418+70dup		intron_variant		1	NM_000534.5	P1

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34013 AN: 148872 Hom.: 3953 Cov.: 25

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.215

GnomAD3 exomes AF: 0.278 AC: 37092 AN: 133226 Hom.: 734 AF XY: 0.276 AC XY: 19556 AN XY: 70758

Gnomad AFR exome AF: 0.336

Gnomad AMR exome AF: 0.324

Gnomad ASJ exome AF: 0.310

Gnomad EAS exome AF: 0.305

Gnomad SAS exome AF: 0.216

Gnomad FIN exome AF: 0.259

Gnomad NFE exome AF: 0.264

Gnomad OTH exome AF: 0.305

GnomAD4 exome AF: 0.208 AC: 250808 AN: 1204904 Hom.: 5612 Cov.: 31 AF XY: 0.206 AC XY: 123130 AN XY: 598466

Gnomad4 AFR exome AF: 0.293

Gnomad4 AMR exome AF: 0.236

Gnomad4 ASJ exome AF: 0.230

Gnomad4 EAS exome AF: 0.238

Gnomad4 SAS exome AF: 0.137

Gnomad4 FIN exome AF: 0.213

Gnomad4 NFE exome AF: 0.208

Gnomad4 OTH exome AF: 0.210

GnomAD4 genome AF: 0.228 AC: 34036 AN: 148962 Hom.: 3958 Cov.: 25 AF XY: 0.226 AC XY: 16445 AN XY: 72616

Gnomad4 AFR AF: 0.290

Gnomad4 AMR AF: 0.252

Gnomad4 ASJ AF: 0.219

Gnomad4 EAS AF: 0.230

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.217

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 30, 2019

- -

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: rs3214425; hg19: chr2-190670539;