Genetic Variant HMCN2:p.Pro4980Pro (chr9-130433393-C-A) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_001291815.2(HMCN2):c.14940C>A(p.Pro4980Pro) variant causes a synonymous 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: 34)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HMCN2
NM_001291815.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0660

Publications

7 publications found

Variant links:

Genes affected

HMCN2 (HGNC:21293): (hemicentin 2) Predicted to enable calcium ion binding activity. Predicted to be an extracellular matrix structural constituent. Predicted to be involved in cell adhesion. Located in collagen-containing extracellular matrix. [provided by Alliance of Genome Resources, Apr 2022]

HMCN2 links:

LOC107987134 (HGNC:):

LOC107987134 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP7

Synonymous conserved (PhyloP=0.066 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001291815.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMCN2	NM_001291815.2	MANE Select	c.14940C>A	p.Pro4980Pro	synonymous	Exon 98 of 98	NP_001278744.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
HMCN2	ENST00000683500.2	MANE Select	c.14940C>A	p.Pro4980Pro	synonymous	Exon 98 of 98	ENSP00000508292.2
HMCN2	ENST00000624552.4	TSL:5	c.14883C>A	p.Pro4961Pro	synonymous	Exon 98 of 98	ENSP00000485357.2
HMCN2	ENST00000623487.1	TSL:2	n.3286C>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1335206

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

657374

African (AFR)

AF:

0.00

AC:

AN:

26924

American (AMR)

AF:

0.00

AC:

AN:

29582

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23466

East Asian (EAS)

AF:

0.00

AC:

AN:

29802

South Asian (SAS)

AF:

0.00

AC:

AN:

74120

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33158

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4244

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1058340

Other (OTH)

AF:

0.00

AC:

AN:

55570

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

2.9

(source)

DANN

Benign

0.90

PhyloP100

0.066

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over