dbSNP rs551741312: HMCN2:p.Pro3256Pro (chr9-130391304-G-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001291815.2(HMCN2):c.9768G>A(p.Pro3256Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000587 in 987,672 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 4 hom., cov: 33)

Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

HMCN2
NM_001291815.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.51

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 9-130391304-G-A is Benign according to our data. Variant chr9-130391304-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2659596.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-4.51 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMCN2	NM_001291815.2	MANE Select	c.9768G>A	p.Pro3256Pro	synonymous	Exon 64 of 98	NP_001278744.1	Q8NDA2-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HMCN2	ENST00000683500.2	MANE Select	c.9768G>A	p.Pro3256Pro	synonymous	Exon 64 of 98	ENSP00000508292.2	Q8NDA2-5
HMCN2	ENST00000624552.4	TSL:5	c.9768G>A	p.Pro3256Pro	synonymous	Exon 64 of 98	ENSP00000485357.2	Q8NDA2-1
HMCN2	ENST00000487727.6	TSL:5	n.861G>A		non_coding_transcript_exon	Exon 7 of 29	ENSP00000485578.1	A0A096LPG1

Frequencies

GnomAD3 genomes

AF:

0.00271

AC:

412

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00890

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00222

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.000956

GnomAD4 exome

AF:

0.000200

AC:

167

AN:

835340

Hom.:

Cov.:

AF XY:

0.000158

AC XY:

AN XY:

385834

show subpopulations

African (AFR)

AF:

0.00769

AC:

122

AN:

15858

American (AMR)

AF:

0.00

AC:

AN:

992

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5158

East Asian (EAS)

AF:

0.00

AC:

AN:

3630

South Asian (SAS)

AF:

0.00

AC:

AN:

16552

European-Finnish (FIN)

AF:

0.00

AC:

AN:

312

Middle Eastern (MID)

AF:

0.00124

AC:

AN:

3228

European-Non Finnish (NFE)

AF:

0.0000394

AC:

AN:

762124

Other (OTH)

AF:

0.000400

AC:

AN:

27486

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00271

AC:

413

AN:

152332

Hom.:

Cov.:

AF XY:

0.00258

AC XY:

192

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.00890

AC:

370

AN:

41582

American (AMR)

AF:

0.00222

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68018

Other (OTH)

AF:

0.000946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

112

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000278

Hom.:

Bravo

AF:

0.00337

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.40

(source)

DANN

Benign

0.88

PhyloP100

-4.5

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over