chr8-79636883-T-C

Variant names:

• chr8-79636883-T-C
• rs1012795099
• NM_007029.4:c.101T>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007029.4(STMN2):​c.101T>C​(p.Ile34Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,212 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: STMN2 NM_007029.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.57

Genes affected

STMN2 (HGNC:10577): (stathmin 2) This gene encodes a member of the stathmin family of phosphoproteins. Stathmin proteins function in microtubule dynamics and signal transduction. The encoded protein plays a regulatory role in neuronal growth and is also thought to be involved in osteogenesis. Reductions in the expression of this gene have been associated with Down's syndrome and Alzheimer's disease. Alternatively spliced transcript variants have been observed for this gene. A pseudogene of this gene is located on the long arm of chromosome 6. [provided by RefSeq, Nov 2010]

LOC105375916 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25663635).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STMN2	NM_007029.4	c.101T>C	p.Ile34Thr	missense_variant	Exon 2 of 5	ENST00000220876.12	NP_008960.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STMN2	ENST00000220876.12	c.101T>C	p.Ile34Thr	missense_variant	Exon 2 of 5	1	NM_007029.4	ENSP00000220876.7
STMN2	ENST00000518111.5	c.101T>C	p.Ile34Thr	missense_variant	Exon 2 of 6	3		ENSP00000429243.1
STMN2	ENST00000518491.1	c.68T>C	p.Ile23Thr	missense_variant	Exon 2 of 5	2		ENSP00000430102.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152212 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152212 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74358

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.101T>C (p.I34T) alteration is located in exon 2 (coding exon 2) of the STMN2 gene. This alteration results from a T to C substitution at nucleotide position 101, causing the isoleucine (I) at amino acid position 34 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.018	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	22
DANN	Benign	0.88
DEOGEN2	Benign	0.18	T;.;T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.057
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.70	T;T;T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.26	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.47	N;N;.
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-1.4	N;N;N
REVEL	Benign	0.11
Sift	Benign	0.42	T;T;T
Sift4G	Benign	0.40	T;T;T
Polyphen		0.016	B;.;.
Vest4		0.52
MutPred		0.41		Loss of stability (P = 0.0059);Loss of stability (P = 0.0059);.;
MVP		0.26
MPC		1.2
ClinPred		0.39	T
GERP RS		5.7
Varity_R		0.074
gMVP		0.48

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: rs1012795099; hg19: chr8-80549118;