2-189877648-A-T

Variant names:

• chr2-189877648-A-T
• rs256552
• ENST00000772194.1:n.265+1762T>A

Variant summary

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

The ENST00000772194.1(ENSG00000300477):​n.265+1762T>A 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: ENSG00000300477 ENST00000772194.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.860
• Publications: 8 publications found

Genes affected

ENSG00000300477 (HGNC:):

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=-0.8).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PMS1	NM_000534.5	c.*212A>T		downstream_gene_variant		ENST00000441310.7	NP_000525.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PMS1	ENST00000441310.7	c.*212A>T		downstream_gene_variant		1	NM_000534.5	ENSP00000406490.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 360418 Hom.: 0 Cov.: 3 AF XY: 0.00 AC XY: 0 AN XY: 187282

African (AFR) AF: 0.00 AC: 0 AN: 11172

American (AMR) AF: 0.00 AC: 0 AN: 15850

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11640

East Asian (EAS) AF: 0.00 AC: 0 AN: 27006

South Asian (SAS) AF: 0.00 AC: 0 AN: 32846

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20468

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1600

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 218100

Other (OTH) AF: 0.00 AC: 0 AN: 21736

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.19
DANN	Benign	0.68
PhyloP100		-0.86

Splicing

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

Other links and lift over

dbSNP: rs256552; hg19: chr2-190742374;