NM_001301056.2:c.717C>T

Variant names:

• chr1-212972799-C-T
• rs141413721
• NM_001301056.2:c.717C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001301056.2(VASH2):​c.717C>T​(p.Tyr239Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,614,106 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0019 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (9 hom.)
• Consequence: VASH2 NM_001301056.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.06
• Publications: 0 publications found

Genes affected

VASH2 (HGNC:25723): (vasohibin 2) Enables actin binding activity; metallocarboxypeptidase activity; and microtubule binding activity. Involved in axon development and proteolysis. Acts upstream of or within cell-cell fusion; positive regulation of angiogenesis; and positive regulation of endothelial cell proliferation. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 1-212972799-C-T is Benign according to our data. Variant chr1-212972799-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2639887.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.06 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001301056.2. 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
	VASH2	NM_001301056.2	MANE Select	c.717C>T	p.Tyr239Tyr	synonymous	Exon 6 of 8	NP_001287985.1	Q86V25-1
	VASH2	NM_024749.5		c.585C>T	p.Tyr195Tyr	synonymous	Exon 4 of 6	NP_079025.2
	VASH2	NM_001136474.3		c.522C>T	p.Tyr174Tyr	synonymous	Exon 7 of 9	NP_001129946.1	Q86V25-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VASH2	ENST00000517399.3	TSL:1 MANE Select	c.717C>T	p.Tyr239Tyr	synonymous	Exon 6 of 8	ENSP00000428324.1	Q86V25-1
	VASH2	ENST00000366965.6	TSL:1	c.585C>T	p.Tyr195Tyr	synonymous	Exon 4 of 6	ENSP00000355932.2	Q86V25-5
	VASH2	ENST00000917486.1		c.903C>T	p.Tyr301Tyr	synonymous	Exon 5 of 7	ENSP00000587545.1

Frequencies

GnomAD3 genomes AF: 0.00194 AC: 295 AN: 152096 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0108

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00247

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00175 AC: 439 AN: 251378 AF XY: 0.00173

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.000298

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00975

Gnomad NFE exome AF: 0.00184

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.00113 AC: 1656 AN: 1461892 Hom.: 9 Cov.: 31 AF XY: 0.00121 AC XY: 877 AN XY: 727246

African (AFR) AF: 0.000179 AC: 6 AN: 33480

American (AMR) AF: 0.000134 AC: 6 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000727 AC: 19 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00884 AC: 472 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000980 AC: 1090 AN: 1112012

Other (OTH) AF: 0.00104 AC: 63 AN: 60396

GnomAD4 genome AF: 0.00194 AC: 295 AN: 152214 Hom.: 2 Cov.: 32 AF XY: 0.00238 AC XY: 177 AN XY: 74414

African (AFR) AF: 0.000144 AC: 6 AN: 41534

American (AMR) AF: 0.000196 AC: 3 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.0108 AC: 114 AN: 10582

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

European-Non Finnish (NFE) AF: 0.00247 AC: 168 AN: 68030

Other (OTH) AF: 0.00189 AC: 4 AN: 2112

Alfa AF: 0.00186 Hom.: 0

Bravo AF: 0.000873

EpiCase AF: 0.00104

EpiControl AF: 0.000652

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	-0.48
CADD	Benign	7.4
DANN	Benign	0.46
PhyloP100		2.1
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs141413721; hg19: chr1-213146141;