chr2-109548083-A-C

Position:

• chr2-109548083-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_144710.5(SEPTIN10):​c.1162-1846T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0643 in 152,176 control chromosomes in the GnomAD database, including 749 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.064 (749 hom., cov: 31)
• Consequence: SEPTIN10 NM_144710.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.321

Genes affected

SEPTIN10 (HGNC:14349): (septin 10) This gene encodes a member of the septin family of cytoskeletal proteins with GTPase activity. This protein localizes to the cytoplasm and nucleus and displays GTP-binding and GTPase activity. A pseudogene for this gene is located on chromosome 8. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2012]

RANBP2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEPTIN10	NM_144710.5	c.1162-1846T>G		intron_variant		ENST00000397712.7	NP_653311.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEPTIN10	ENST00000397712.7	c.1162-1846T>G		intron_variant		1	NM_144710.5	ENSP00000380824

Frequencies

GnomAD3 genomes AF: 0.0642 AC: 9760 AN: 152060 Hom.: 739 Cov.: 31

Gnomad AFR AF: 0.0505

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.0534

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.0845

Gnomad FIN AF: 0.0533

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0291

Gnomad OTH AF: 0.0688

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

GnomAD4 genome AF: 0.0643 AC: 9786 AN: 152176 Hom.: 749 Cov.: 31 AF XY: 0.0689 AC XY: 5128 AN XY: 74402

Gnomad4 AFR AF: 0.0505

Gnomad4 AMR AF: 0.205

Gnomad4 ASJ AF: 0.0534

Gnomad4 EAS AF: 0.240

Gnomad4 SAS AF: 0.0842

Gnomad4 FIN AF: 0.0533

Gnomad4 NFE AF: 0.0291

Gnomad4 OTH AF: 0.0676

Alfa AF: 0.0657 Hom.: 437

Bravo AF: 0.0813

Asia WGS AF: 0.149 AC: 517 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.2
DANN	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs10496431; hg19: chr2-110305660;