2-189867926-CCA-ACG

Variant names:

• chr2-189867926-CCA-ACG
• NM_000534.5:c.2470_2472delCCAinsACG
• PMS1 p.Pro824Thr

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_000534.5(PMS1):​c.2470_2472delCCAinsACG​(p.Pro824Thr) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PMS1 NM_000534.5 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.31
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• Lynch syndrome

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000300477 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000534.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PMS1	NM_000534.5	MANE Select	c.2470_2472delCCAinsACG	p.Pro824Thr	missense splice_region	N/A	NP_000525.1	P54277-1
	PMS1	NM_001321045.2		c.2470_2472delCCAinsACG	p.Pro824Thr	missense splice_region	N/A	NP_001307974.1	P54277-1
	PMS1	NM_001321047.2		c.2470_2472delCCAinsACG	p.Pro824Thr	missense splice_region	N/A	NP_001307976.1	P54277-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PMS1	ENST00000441310.7	TSL:1 MANE Select	c.2470_2472delCCAinsACG	p.Pro824Thr	missense splice_region	N/A	ENSP00000406490.3	P54277-1
	PMS1	ENST00000409593.5	TSL:1	c.1339_1341delCCAinsACG	p.Pro447Thr	missense splice_region	N/A	ENSP00000387169.1	P54277-4
	PMS1	ENST00000424059.1	TSL:1	n.1971+3952_1971+3954delCCAinsACG		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr2-190732652;