NM_001291815.2:c.9069C>T

Variant names:

• chr9-130384761-C-T
• rs61734919
• NM_001291815.2:c.9069C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_001291815.2(HMCN2):​c.9069C>T​(p.Ala3023Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00604 in 1,303,284 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0057 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0061 (30 hom.)
• Consequence: HMCN2 NM_001291815.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.23
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.041).
• BP6: Variant 9-130384761-C-T is Benign according to our data. Variant chr9-130384761-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2659595.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.23 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 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.9069C>T	p.Ala3023Ala	synonymous	Exon 59 of 98	NP_001278744.1	Q8NDA2-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMCN2	ENST00000683500.2	MANE Select	c.9069C>T	p.Ala3023Ala	synonymous	Exon 59 of 98	ENSP00000508292.2	Q8NDA2-5
	HMCN2	ENST00000624552.4	TSL:5	c.9069C>T	p.Ala3023Ala	synonymous	Exon 59 of 98	ENSP00000485357.2	Q8NDA2-1
	HMCN2	ENST00000487727.6	TSL:5	n.162C>T		non_coding_transcript_exon	Exon 2 of 29	ENSP00000485578.1	A0A096LPG1

Frequencies

GnomAD3 genomes AF: 0.00569 AC: 866 AN: 152148 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00118

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00648

Gnomad ASJ AF: 0.00837

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00870

Gnomad FIN AF: 0.0175

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00663

Gnomad OTH AF: 0.00480

GnomAD2 exomes AF: 0.00612 AC: 906 AN: 148122 AF XY: 0.00653

Gnomad AFR exome AF: 0.00103

Gnomad AMR exome AF: 0.00391

Gnomad ASJ exome AF: 0.00848

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0149

Gnomad NFE exome AF: 0.00616

Gnomad OTH exome AF: 0.00768

GnomAD4 exome AF: 0.00608 AC: 7002 AN: 1151018 Hom.: 30 Cov.: 32 AF XY: 0.00623 AC XY: 3518 AN XY: 564458

African (AFR) AF: 0.000983 AC: 24 AN: 24418

American (AMR) AF: 0.00361 AC: 102 AN: 28268

Ashkenazi Jewish (ASJ) AF: 0.00916 AC: 146 AN: 15940

East Asian (EAS) AF: 0.00 AC: 0 AN: 12842

South Asian (SAS) AF: 0.00604 AC: 460 AN: 76204

European-Finnish (FIN) AF: 0.0148 AC: 392 AN: 26426

Middle Eastern (MID) AF: 0.00568 AC: 25 AN: 4404

European-Non Finnish (NFE) AF: 0.00610 AC: 5614 AN: 920904

Other (OTH) AF: 0.00574 AC: 239 AN: 41612

GnomAD4 genome AF: 0.00569 AC: 867 AN: 152266 Hom.: 2 Cov.: 32 AF XY: 0.00663 AC XY: 494 AN XY: 74462

African (AFR) AF: 0.00118 AC: 49 AN: 41550

American (AMR) AF: 0.00660 AC: 101 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00837 AC: 29 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00871 AC: 42 AN: 4822

European-Finnish (FIN) AF: 0.0175 AC: 186 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00662 AC: 450 AN: 68020

Other (OTH) AF: 0.00475 AC: 10 AN: 2104

Alfa AF: 0.00561 Hom.: 2

Bravo AF: 0.00473

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	4.1
DANN	Benign	0.64
PhyloP100		-2.2

Splicing

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

Other links and lift over

dbSNP: rs61734919; hg19: chr9-133260148;