10-86942767-G-T

Variant names:

• chr10-86942767-G-T
• rs1171422014
• NM_024756.3:c.2017C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_024756.3(MMRN2):​c.2017C>A​(p.Arg673Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000164 in 1,221,234 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: MMRN2 NM_024756.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.225
• Publications: 0 publications found

Genes affected

MMRN2 (HGNC:19888): (multimerin 2) This gene encodes a protein belonging to the member of elastin microfibril interface-located (EMILIN) protein family. This family member is an extracellular matrix glycoprotein that can interfere with tumor angiogenesis and growth. It serves as a transforming growth factor beta antagonist and can interfere with the VEGF-A/VEGFR2 pathway. A related pseudogene has been identified on chromosome 6. [provided by RefSeq, Aug 2012]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP7: Synonymous conserved (PhyloP=0.225 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024756.3. 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
	MMRN2	NM_024756.3	MANE Select	c.2017C>A	p.Arg673Arg	synonymous	Exon 6 of 7	NP_079032.2	Q9H8L6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMRN2	ENST00000372027.10	TSL:1 MANE Select	c.2017C>A	p.Arg673Arg	synonymous	Exon 6 of 7	ENSP00000361097.4	Q9H8L6
	MMRN2	ENST00000896191.1		c.2047C>A	p.Arg683Arg	synonymous	Exon 6 of 7	ENSP00000566250.1
	MMRN2	ENST00000896187.1		c.2017C>A	p.Arg673Arg	synonymous	Exon 7 of 8	ENSP00000566246.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000164 AC: 2 AN: 1221234 Hom.: 0 Cov.: 33 AF XY: 0.00000169 AC XY: 1 AN XY: 592542

African (AFR) AF: 0.0000420 AC: 1 AN: 23788

American (AMR) AF: 0.00 AC: 0 AN: 12308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16914

East Asian (EAS) AF: 0.00 AC: 0 AN: 27260

South Asian (SAS) AF: 0.00 AC: 0 AN: 54990

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29876

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4082

European-Non Finnish (NFE) AF: 9.98e-7 AC: 1 AN: 1002030

Other (OTH) AF: 0.00 AC: 0 AN: 49986

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.9
DANN	Benign	0.86
PhyloP100		0.23

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: rs1171422014; hg19: chr10-88702524;