2-189817925-A-G

Position:

• chr2-189817925-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000534.5(PMS1):​c.419-92A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0084 in 955,896 control chromosomes in the GnomAD database, including 424 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.033 (281 hom., cov: 32)
  • Exomes 𝑓: 0.0037 (143 hom.)
• Consequence: PMS1 NM_000534.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.488

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 2-189817925-A-G is Benign according to our data. Variant chr2-189817925-A-G is described in ClinVar as [Benign]. Clinvar id is 1182485.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PMS1	NM_000534.5	c.419-92A>G		intron_variant		ENST00000441310.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PMS1	ENST00000441310.7	c.419-92A>G		intron_variant		1	NM_000534.5	P1

Frequencies

GnomAD3 genomes AF: 0.0330 AC: 5023 AN: 152158 Hom.: 281 Cov.: 32

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0122

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.0249

GnomAD4 exome AF: 0.00373 AC: 2996 AN: 803620 Hom.: 143 AF XY: 0.00309 AC XY: 1301 AN XY: 421454

Gnomad4 AFR exome AF: 0.112

Gnomad4 AMR exome AF: 0.00605

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000245

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000121

Gnomad4 OTH exome AF: 0.00822

GnomAD4 genome AF: 0.0330 AC: 5031 AN: 152276 Hom.: 281 Cov.: 32 AF XY: 0.0311 AC XY: 2317 AN XY: 74470

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.0122

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000323

Gnomad4 OTH AF: 0.0246

Alfa AF: 0.0157 Hom.: 17

Bravo AF: 0.0376

Asia WGS AF: 0.00577 AC: 21 AN: 3478

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

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.4
DANN	Benign	0.68

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: rs5743042; hg19: chr2-190682651;