17-46929567-AC-GT

Variant names:

• chr17-46929567-AC-GT
• NM_004287.5:c.77_78delACinsGT
• GOSR2 p.Asp26Gly

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_004287.5(GOSR2):​c.77_78delACinsGT​(p.Asp26Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GOSR2 NM_004287.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.97
• Publications: 0 publications found

Genes affected

GOSR2 (HGNC:4431): (golgi SNAP receptor complex member 2) This gene encodes a trafficking membrane protein which transports proteins among the medial- and trans-Golgi compartments. Due to its chromosomal location and trafficking function, this gene may be involved in familial essential hypertension. [provided by RefSeq, Mar 2016]

ENSG00000262633 (HGNC:):

LRRC37A2 (HGNC:32404): (leucine rich repeat containing 37 member A2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004287.5. 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
	GOSR2	NM_004287.5	MANE Select	c.77_78delACinsGT	p.Asp26Gly	missense	N/A	NP_004278.2
	GOSR2	NM_001321133.2		c.77_78delACinsGT	p.Asp26Gly	missense	N/A	NP_001308062.1	I3NI02
	GOSR2	NM_054022.4		c.77_78delACinsGT	p.Asp26Gly	missense	N/A	NP_473363.1	O14653-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOSR2	ENST00000640051.2	TSL:1 MANE Select	c.77_78delACinsGT	p.Asp26Gly	missense	N/A	ENSP00000492751.1	O14653-1
	GOSR2	ENST00000225567.9	TSL:1	c.77_78delACinsGT	p.Asp26Gly	missense	N/A	ENSP00000225567.4	O14653-2
	GOSR2	ENST00000640621.1	TSL:1	c.77_78delACinsGT	p.Asp26Gly	missense	N/A	ENSP00000492830.1	O14653-3

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.0

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr17-45006933;