2-189784590-G-C

Position:

• chr2-189784590-G-C

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.-24G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 153,002 control chromosomes in the GnomAD database, including 4,237 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (4226 hom., cov: 33)
  • Exomes 𝑓: 0.18 (11 hom.)
• Consequence: PMS1 NM_000534.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.285

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=-0.66).
• BP6: Variant 2-189784590-G-C is Benign according to our data. Variant chr2-189784590-G-C is described in ClinVar as [Benign]. Clinvar id is 1292222.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PMS1	NM_000534.5	c.-24G>C		5_prime_UTR_variant	1/13	ENST00000441310.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PMS1	ENST00000441310.7	c.-24G>C		5_prime_UTR_variant	1/13	1	NM_000534.5	P1

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34723 AN: 152102 Hom.: 4218 Cov.: 33

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.219

GnomAD4 exome AF: 0.179 AC: 140 AN: 782 Hom.: 11 Cov.: 0 AF XY: 0.162 AC XY: 69 AN XY: 426

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.200

Gnomad4 EAS exome AF: 0.0882

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.190

Gnomad4 NFE exome AF: 0.178

Gnomad4 OTH exome AF: 0.146

GnomAD4 genome AF: 0.228 AC: 34750 AN: 152220 Hom.: 4226 Cov.: 33 AF XY: 0.226 AC XY: 16796 AN XY: 74440

Gnomad4 AFR AF: 0.296

Gnomad4 AMR AF: 0.252

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.226

Gnomad4 SAS AF: 0.120

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.197

Gnomad4 OTH AF: 0.221

Alfa AF: 0.134 Hom.: 254

Bravo AF: 0.236

Asia WGS AF: 0.201 AC: 699 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	-0.66
CADD	Benign	10
DANN	Benign	0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs5742933; hg19: chr2-190649316; COSMIC: COSV57877498; COSMIC: COSV57877498;