2-189826225-G-C

Position:

• chr2-189826225-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000534.5(PMS1):​c.582+8045G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 151,976 control chromosomes in the GnomAD database, including 19,528 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.44 (19528 hom., cov: 32)
• Consequence: PMS1 NM_000534.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.15

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.842 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PMS1	NM_000534.5	c.582+8045G>C		intron_variant		ENST00000441310.7	NP_000525.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PMS1	ENST00000441310.7	c.582+8045G>C		intron_variant		1	NM_000534.5	ENSP00000406490.3

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66350 AN: 151856 Hom.: 19471 Cov.: 32

Gnomad AFR AF: 0.848

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.401

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.437 AC: 66450 AN: 151976 Hom.: 19528 Cov.: 32 AF XY: 0.433 AC XY: 32131 AN XY: 74252

Gnomad4 AFR AF: 0.849

Gnomad4 AMR AF: 0.347

Gnomad4 ASJ AF: 0.272

Gnomad4 EAS AF: 0.282

Gnomad4 SAS AF: 0.238

Gnomad4 FIN AF: 0.301

Gnomad4 NFE AF: 0.267

Gnomad4 OTH AF: 0.402

Alfa AF: 0.219 Hom.: 574

Bravo AF: 0.457

Asia WGS AF: 0.317 AC: 1104 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.23
DANN	Benign	0.57

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: rs1233291; hg19: chr2-190690951;