rs2987346

Positions:

• chr13-29026278-A-G

Variant summary

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

The NM_001033602.4(MTUS2):​c.1580A>G​(p.Asp527Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0344 in 1,613,792 control chromosomes in the GnomAD database, including 3,412 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.093 (1506 hom., cov: 32)
  • Exomes 𝑓: 0.028 (1906 hom.)
• Consequence: MTUS2 NM_001033602.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.880

Genes affected

MTUS2 (HGNC:20595): (microtubule associated scaffold protein 2) Enables microtubule binding activity and protein homodimerization activity. Part of nucleus. Colocalizes with centrosome and cytoplasmic microtubule. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006790191).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTUS2	NM_001033602.4	c.1580A>G	p.Asp527Gly	missense_variant	3/16	ENST00000612955.6	NP_001028774.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTUS2	ENST00000612955.6	c.1580A>G	p.Asp527Gly	missense_variant	3/16	5	NM_001033602.4	ENSP00000483729.2

Frequencies

GnomAD3 genomes AF: 0.0928 AC: 14096 AN: 151970 Hom.: 1488 Cov.: 32

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0523

Gnomad ASJ AF: 0.0268

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.0193

Gnomad FIN AF: 0.0112

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0203

Gnomad OTH AF: 0.0882

GnomAD3 exomes AF: 0.0442 AC: 10999 AN: 249128 Hom.: 745 AF XY: 0.0391 AC XY: 5284 AN XY: 135142

Gnomad AFR exome AF: 0.275

Gnomad AMR exome AF: 0.0292

Gnomad ASJ exome AF: 0.0327

Gnomad EAS exome AF: 0.123

Gnomad SAS exome AF: 0.0135

Gnomad FIN exome AF: 0.0115

Gnomad NFE exome AF: 0.0205

Gnomad OTH exome AF: 0.0374

GnomAD4 exome AF: 0.0283 AC: 41322 AN: 1461704 Hom.: 1906 Cov.: 31 AF XY: 0.0272 AC XY: 19749 AN XY: 727134

Gnomad4 AFR exome AF: 0.276

Gnomad4 AMR exome AF: 0.0327

Gnomad4 ASJ exome AF: 0.0314

Gnomad4 EAS exome AF: 0.0978

Gnomad4 SAS exome AF: 0.0132

Gnomad4 FIN exome AF: 0.0110

Gnomad4 NFE exome AF: 0.0189

Gnomad4 OTH exome AF: 0.0470

GnomAD4 genome AF: 0.0930 AC: 14147 AN: 152088 Hom.: 1506 Cov.: 32 AF XY: 0.0908 AC XY: 6752 AN XY: 74330

Gnomad4 AFR AF: 0.262

Gnomad4 AMR AF: 0.0523

Gnomad4 ASJ AF: 0.0268

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.0189

Gnomad4 FIN AF: 0.0112

Gnomad4 NFE AF: 0.0203

Gnomad4 OTH AF: 0.0882

Alfa AF: 0.0383 Hom.: 713

Bravo AF: 0.106

TwinsUK AF: 0.0208 AC: 77

ALSPAC AF: 0.0166 AC: 64

ESP6500AA AF: 0.250 AC: 1010

ESP6500EA AF: 0.0190 AC: 159

ExAC AF: 0.0473 AC: 5717

Asia WGS AF: 0.0860 AC: 298 AN: 3478

EpiCase AF: 0.0242

EpiControl AF: 0.0260

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.9
DANN	Benign	0.78
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.47	T
MetaRNN	Benign	0.0068	T
MetaSVM	Benign	-0.90	T
PrimateAI	Benign	0.25	T
Sift4G	Benign	0.15	T
Vest4		0.035
ClinPred		0.00085	T
GERP RS		1.1

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2987346; hg19: chr13-29600415; COSMIC: COSV70914954;