NM_006949.4:c.-38delG

Variant names:

• chr19-7637109-TG-T
• rs886038578
• NM_006949.4:c.-38delG

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_006949.4(STXBP2):​c.-38delG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000046 in 1,085,956 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000046 (0 hom.)
• Consequence: STXBP2 NM_006949.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.52
• Publications: 0 publications found

Genes affected

STXBP2 (HGNC:11445): (syntaxin binding protein 2) This gene encodes a member of the STXBP/unc-18/SEC1 family. The encoded protein is involved in intracellular trafficking, control of SNARE (soluble NSF attachment protein receptor) complex assembly, and the release of cytotoxic granules by natural killer cells. Mutations in this gene are associated with familial hemophagocytic lymphohistiocytosis. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Jan 2013]

ENSG00000268400 (HGNC:):

PCP2 (HGNC:30209): (Purkinje cell protein 2) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of catalytic activity. Predicted to act upstream of or within rhodopsin mediated signaling pathway. Predicted to be located in neuronal cell body. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 19-7637109-TG-T is Benign according to our data. Variant chr19-7637109-TG-T is described in ClinVar as Likely_benign. ClinVar VariationId is 260081.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006949.4. 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
	STXBP2	NM_006949.4	MANE Select	c.-38delG		5_prime_UTR	Exon 1 of 19	NP_008880.2
	STXBP2	NM_001272034.2		c.-38delG		5_prime_UTR	Exon 1 of 19	NP_001258963.1
	STXBP2	NM_001127396.3		c.-38delG		5_prime_UTR	Exon 1 of 19	NP_001120868.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STXBP2	ENST00000221283.10	TSL:1 MANE Select	c.-38delG		5_prime_UTR	Exon 1 of 19	ENSP00000221283.4
	ENSG00000268400	ENST00000698368.1		n.*140+77delG		intron	N/A	ENSP00000513686.1
	STXBP2	ENST00000595950.5	TSL:5	c.-38delG		5_prime_UTR	Exon 1 of 6	ENSP00000471161.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000460 AC: 5 AN: 1085956 Hom.: 0 Cov.: 31 AF XY: 0.00000585 AC XY: 3 AN XY: 512996

African (AFR) AF: 0.00 AC: 0 AN: 22908

American (AMR) AF: 0.00 AC: 0 AN: 8396

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14354

East Asian (EAS) AF: 0.00 AC: 0 AN: 26506

South Asian (SAS) AF: 0.000152 AC: 3 AN: 19800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27192

Middle Eastern (MID) AF: 0.000312 AC: 1 AN: 3210

European-Non Finnish (NFE) AF: 0.00000109 AC: 1 AN: 919888

Other (OTH) AF: 0.00 AC: 0 AN: 43702

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.5

Splicing

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

Other links and lift over

dbSNP: rs886038578; hg19: chr19-7701995;