8-79654923-G-A

Variant names:

• chr8-79654923-G-A
• rs1236533784
• NM_007029.4:c.341G>A

Variant summary

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

The NM_007029.4(STMN2):​c.341G>A​(p.Arg114Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: STMN2 NM_007029.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 10.0

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STMN2	NM_007029.4	c.341G>A	p.Arg114Gln	missense_variant	Exon 4 of 5	ENST00000220876.12	NP_008960.2
STMN2	NM_001199214.2	c.341G>A	p.Arg114Gln	missense_variant	Exon 4 of 6		NP_001186143.1
STMN2	XM_005251142.3	c.326G>A	p.Arg109Gln	missense_variant	Exon 5 of 6		XP_005251199.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STMN2	ENST00000220876.12	c.341G>A	p.Arg114Gln	missense_variant	Exon 4 of 5	1	NM_007029.4	ENSP00000220876.7
STMN2	ENST00000518111.5	c.341G>A	p.Arg114Gln	missense_variant	Exon 4 of 6	3		ENSP00000429243.1
STMN2	ENST00000518491.1	c.308G>A	p.Arg103Gln	missense_variant	Exon 4 of 5	2		ENSP00000430102.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 13, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.341G>A (p.R114Q) alteration is located in exon 4 (coding exon 4) of the STMN2 gene. This alteration results from a G to A substitution at nucleotide position 341, causing the arginine (R) at amino acid position 114 to be replaced by a glutamine (Q). 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	0.21
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.23	T;.;T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D;D;D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.56	D;D;D
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.5	M;M;.
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-2.5	D;N;D
REVEL	Uncertain	0.36
Sift	Benign	0.24	T;T;T
Sift4G	Benign	0.22	T;T;T
Polyphen		0.79	P;.;.
Vest4		0.74
MVP		0.46
MPC		1.2
ClinPred		0.90	D
GERP RS		5.8
Varity_R		0.41
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: rs1236533784; hg19: chr8-80567158; COSMIC: COSV55223931;