Variant chr2-189795957-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000534.5(PMS1):c.315+6G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0352 in 1,578,098 control chromosomes in the GnomAD database, including 1,236 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.031 ( 113 hom., cov: 32)

Exomes 𝑓: 0.036 ( 1123 hom. )

Consequence

PMS1
NM_000534.5 splice_donor_region, intron

Scores

Splicing: ADA: 0.0001624

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.470

Variant links:

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]

PMS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 2-189795957-G-A is Benign according to our data. Variant chr2-189795957-G-A is described in ClinVar as [Benign]. Clinvar id is 1274521.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PMS1	NM_000534.5 linkuse as main transcript	c.315+6G>A		splice_donor_region_variant, intron_variant		ENST00000441310.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PMS1	ENST00000441310.7 linkuse as main transcript	c.315+6G>A		splice_donor_region_variant, intron_variant		1	NM_000534.5	P1	P54277-1

Frequencies

GnomAD3 genomes

AF:

0.0311

AC:

4727

AN:

152130

Hom.:

113

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00729

Gnomad AMI

AF:

0.0296

Gnomad AMR

AF:

0.0564

Gnomad ASJ

AF:

0.0150

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.0122

Gnomad FIN

AF:

0.0741

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0380

Gnomad OTH

AF:

0.0234

GnomAD3 exomes

AF:

0.0340

AC:

8538

AN:

250968

Hom.:

218

AF XY:

0.0326

AC XY:

4426

AN XY:

135756

show subpopulations

Gnomad AFR exome

AF:

0.00714

Gnomad AMR exome

AF:

0.0544

Gnomad ASJ exome

AF:

0.0110

Gnomad EAS exome

AF:

0.000544

Gnomad SAS exome

AF:

0.0111

Gnomad FIN exome

AF:

0.0762

Gnomad NFE exome

AF:

0.0374

Gnomad OTH exome

AF:

0.0326

GnomAD4 exome

AF:

0.0357

AC:

50856

AN:

1425850

Hom.:

1123

Cov.:

AF XY:

0.0350

AC XY:

24893

AN XY:

711716

show subpopulations

Gnomad4 AFR exome

AF:

0.00589

Gnomad4 AMR exome

AF:

0.0542

Gnomad4 ASJ exome

AF:

0.0117

Gnomad4 EAS exome

AF:

0.000632

Gnomad4 SAS exome

AF:

0.0127

Gnomad4 FIN exome

AF:

0.0734

Gnomad4 NFE exome

AF:

0.0381

Gnomad4 OTH exome

AF:

0.0293

GnomAD4 genome

AF:

0.0310

AC:

4724

AN:

152248

Hom.:

113

Cov.:

AF XY:

0.0322

AC XY:

2396

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.00727

Gnomad4 AMR

AF:

0.0562

Gnomad4 ASJ

AF:

0.0150

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.0120

Gnomad4 FIN

AF:

0.0741

Gnomad4 NFE

AF:

0.0380

Gnomad4 OTH

AF:

0.0232

Alfa

AF:

0.0331

Hom.:

Bravo

AF:

0.0273

Asia WGS

AF:

0.00693

AC:

AN:

3478

EpiCase

AF:

0.0324

EpiControl

AF:

0.0331

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00016

dbscSNV1_RF

Benign

0.014

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over