2-189784514-G-C

Variant names:

• chr2-189784514-G-C
• rs5742932
• NM_000534.5:c.-100G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000534.5(PMS1):​c.-100G>C variant causes a 5 prime UTR 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: 33)
• Consequence: PMS1 NM_000534.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0220
• Publications: 3 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]

ORMDL1 (HGNC:16036): (ORMDL sphingolipid biosynthesis regulator 1) Involved in ceramide metabolic process. Acts upstream of or within negative regulation of ceramide biosynthetic process. Located in endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.-100G>C		5_prime_UTR	Exon 1 of 13	NP_000525.1	P54277-1
	PMS1	NM_001321045.2		c.-226G>C		5_prime_UTR	Exon 1 of 14	NP_001307974.1	P54277-1
	PMS1	NM_001321047.2		c.-277G>C		5_prime_UTR	Exon 1 of 13	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.-100G>C		5_prime_UTR	Exon 1 of 13	ENSP00000406490.3	P54277-1
	PMS1	ENST00000374826.8	TSL:1	c.-100G>C		5_prime_UTR	Exon 1 of 5	ENSP00000363959.4	Q5XG96
	PMS1	ENST00000921104.1		c.-100G>C		5_prime_UTR	Exon 1 of 14	ENSP00000591163.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	14
DANN	Benign	0.57
PhyloP100		-0.022
PromoterAI		0.12	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.41		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.41		Position offset: 18

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

Other links and lift over

dbSNP: rs5742932; hg19: chr2-190649240;