2-189817906-G-T

Variant names:

• chr2-189817906-G-T
• rs3791773
• NM_000534.5:c.419-111G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000534.5(PMS1):​c.419-111G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PMS1 NM_000534.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.758
• Publications: 11 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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

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.419-111G>T		intron	N/A	NP_000525.1	P54277-1
	PMS1	NM_001321045.2		c.419-111G>T		intron	N/A	NP_001307974.1	P54277-1
	PMS1	NM_001321047.2		c.419-111G>T		intron	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.419-111G>T		intron	N/A	ENSP00000406490.3	P54277-1
	PMS1	ENST00000424059.1	TSL:1	n.419-111G>T		intron	N/A
	PMS1	ENST00000921104.1		c.419-111G>T		intron	N/A	ENSP00000591163.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 643920 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 343486

African (AFR) AF: 0.00 AC: 0 AN: 17572

American (AMR) AF: 0.00 AC: 0 AN: 33672

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19898

East Asian (EAS) AF: 0.00 AC: 0 AN: 33218

South Asian (SAS) AF: 0.00 AC: 0 AN: 64816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45862

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2512

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 394100

Other (OTH) AF: 0.00 AC: 0 AN: 32270

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 230

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	11
DANN	Benign	0.61
PhyloP100		0.76
PromoterAI		0.0095	Neutral

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

Other links and lift over

dbSNP: rs3791773; hg19: chr2-190682632;