20-35201339-C-G

Variant names:

Variant summary

Our verdict is The variant received -2 classification points (ACMG Germline Pathogenicity v2019). PM2BP4_Strong

The NM_001355008.2(MMP24-AS1-EDEM2):c.-102+16473G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. Note: NM_001355008.2 is not a MANE Select or MANE Plus Clinical transcript for MMP24-AS1-EDEM2; the reported annotation may differ from that of the MANE-designated reference transcript for this gene. The variant has a gnomAD grpmax filtering allele frequency (95% CI) of 0.0000147, indicating it is observed in the general population. Note: a gnomAD entry for this variant shows a statistical allele-bias signature, consistent with mosaic/somatic contamination (e.g. age-related clonal hematopoiesis) rather than true inherited population frequency — this frequency should not be read as evidence of a common, benign germline variant. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

MMP24-AS1-EDEM2
NM_001355008.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.41

Publications

24 publications found

Variant links:

Genes affected

MMP24-AS1-EDEM2 (HGNC:):

MMP24-AS1-EDEM2 links:

PROCR (HGNC:9452): (protein C receptor) The protein encoded by this gene is a receptor for activated protein C, a serine protease activated by and involved in the blood coagulation pathway. The encoded protein is an N-glycosylated type I membrane protein that enhances the activation of protein C. Mutations in this gene have been associated with venous thromboembolism and myocardial infarction, as well as with late fetal loss during pregnancy. The encoded protein may also play a role in malarial infection and has been associated with cancer. [provided by RefSeq, Jul 2013]

PROCR links:

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new If you want to explore the variant's impact on the transcript NM_001355008.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

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

Show applied only (2)

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	PM2Absent/extremely low in population databases		Very rare in gnomAD for AR/unknown gene (popmax AF < threshold/10) — PM2; GnomAD popmax AF = 0.0000147 — very rare for unknown gene (threshold 0.001) — PM2 moderate.
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); No splicing predictor data available.; Germline computational verdict: benign (Strong).

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_001355008.2. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	MMP24-AS1-EDEM2 NM_001355008.2		c.-102+16473G>C	intron	Intron 4 of 14	Prot: NP_001341937.1

MMP24-AS1-EDEM2 NM_001355008.2

HGVSc / HGVSpc.-102+16473G>C

Exon rankIntron 4 of 14

intron

Prot: NP_001341937.1

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	PROCR ENST00000635377.1	TSL:5	c.629-14554C>G	intron	Intron 3 of 3	Prot: ENSP00000489117.1 UniProt: A0A0U1RQQ4
	PROCR ENST00000634509.1	TSL:3	c.95-14554C>G	intron	Intron 1 of 1	Prot: ENSP00000489456.1 UniProt: A0A0U1RRC4

PROCR ENST00000635377.1

TSL:5

HGVSc / HGVSpc.629-14554C>G

Exon rankIntron 3 of 3

intron

Prot: ENSP00000489117.1UniProt: A0A0U1RQQ4

PROCR ENST00000634509.1

TSL:3

HGVSc / HGVSpc.95-14554C>G

Exon rankIntron 1 of 1

intron

Prot: ENSP00000489456.1UniProt: A0A0U1RRC4

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 4 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.00000658	AC:1	Hom:0	AN:151938	Cov:32
GnomAD4 genome Warning	AF: 0.00000658	AC:1	Hom:0	AN:151938	Cov:32
TOPMed (Bravo)	AF: 0.00000378	AC:	Hom:	AN:	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.00	AC:0	Hom:20360	AN:219828	Cov:

Showing 4 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score
AlphaGenome AVI	Benign	0.35
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.8
DANN	Benign	0.53
GPN-Star LLR	N/A	4.8
GPN-Star score	N/A	0.15
PhyloP100	Benign	-1.4

Showing 7 of 7 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0

Showing 1 of 1 scores

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.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational Scores

Splicing Scores

MaveDB functional evidence ?

Publications

Other links and lift over

MaveDB functional evidence