rs2104533

Variant names:

• chr9-92528174-G-A
• rs2104533
• NM_001393.4:c.-27-5281C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001393.4(ECM2):​c.-27-5281C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 152,068 control chromosomes in the GnomAD database, including 15,617 homozygotes. 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: 𝑓 0.42 (15602 hom., cov: 31)
  • Exomes 𝑓: 0.37 (15 hom.)
• Consequence: ECM2 NM_001393.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.544
• Publications: 11 publications found

Genes affected

ECM2 (HGNC:3154): (extracellular matrix protein 2) ECM2 encodes extracellular matrix protein 2, so named because it shares extensive similarity with known extracelluar matrix proteins. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2010]

CENPP (HGNC:32933): (centromere protein P) CENPP is a subunit of a CENPH (MIM 605607)-CENPI (MIM 300065)-associated centromeric complex that targets CENPA (MIM 117139) to centromeres and is required for proper kinetochore function and mitotic progression (Okada et al., 2006 [PubMed 16622420]).[supplied by OMIM, Mar 2008]

MIR4670 (HGNC:41862): (microRNA 4670) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ECM2	NM_001393.4	c.-27-5281C>T		intron_variant	Intron 1 of 9	ENST00000344604.10	NP_001384.1
CENPP	NM_001012267.3	c.565-83140G>A		intron_variant	Intron 5 of 7	ENST00000375587.8	NP_001012267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ECM2	ENST00000344604.10	c.-27-5281C>T		intron_variant	Intron 1 of 9	1	NM_001393.4	ENSP00000344758.5
CENPP	ENST00000375587.8	c.565-83140G>A		intron_variant	Intron 5 of 7	1	NM_001012267.3	ENSP00000364737.3

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63598 AN: 151742 Hom.: 15575 Cov.: 31

Gnomad AFR AF: 0.676

Gnomad AMI AF: 0.619

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.420

GnomAD4 exome AF: 0.365 AC: 76 AN: 208 Hom.: 15 AF XY: 0.389 AC XY: 42 AN XY: 108

African (AFR) AF: 0.625 AC: 5 AN: 8

American (AMR) AF: 0.00 AC: 0 AN: 4

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 1 AN: 4

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.167 AC: 1 AN: 6

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AF: 0.250 AC: 1 AN: 4

European-Non Finnish (NFE) AF: 0.372 AC: 61 AN: 164

Other (OTH) AF: 0.375 AC: 6 AN: 16

GnomAD4 genome AF: 0.419 AC: 63666 AN: 151860 Hom.: 15602 Cov.: 31 AF XY: 0.409 AC XY: 30348 AN XY: 74248

African (AFR) AF: 0.676 AC: 28015 AN: 41414

American (AMR) AF: 0.305 AC: 4654 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 1524 AN: 3470

East Asian (EAS) AF: 0.132 AC: 678 AN: 5138

South Asian (SAS) AF: 0.240 AC: 1157 AN: 4820

European-Finnish (FIN) AF: 0.273 AC: 2882 AN: 10566

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.341 AC: 23159 AN: 67870

Other (OTH) AF: 0.416 AC: 877 AN: 2108

Alfa AF: 0.396 Hom.: 2174

Bravo AF: 0.435

Asia WGS AF: 0.240 AC: 835 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.53
DANN	Benign	0.55
PhyloP100		-0.54
Mutation Taster		=100/0	polymorphism (auto)

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: rs2104533; hg19: chr9-95290456;