rs9384296

Positions:

• chr6-155209710-G-A
• chr6-155209710-G-T

Variant summary

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

The NM_012454.4(TIAM2):​c.3065-1494G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,144 control chromosomes in the GnomAD database, including 2,182 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 0.16 (2182 hom., cov: 32)
• Consequence: TIAM2 NM_012454.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0460

Genes affected

TIAM2 (HGNC:11806): (TIAM Rac1 associated GEF 2) This gene encodes a guanine nucleotide exchange factor. A highly similar mouse protein specifically activates ras-related C3 botulinum substrate 1, converting this Rho-like guanosine triphosphatase (GTPase) from a guanosine diphosphate-bound inactive state to a guanosine triphosphate-bound active state. The encoded protein may play a role in neural cell development. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TIAM2	NM_012454.4	c.3065-1494G>A		intron_variant		ENST00000682666.1
TIAM2	NM_001384546.1	c.3065-1494G>A		intron_variant
TIAM2	NM_001384547.1	c.3065-1494G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TIAM2	ENST00000682666.1	c.3065-1494G>A		intron_variant			NM_012454.4	A2

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24568 AN: 152026 Hom.: 2180 Cov.: 32

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.0838

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.132

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

GnomAD4 genome AF: 0.162 AC: 24585 AN: 152144 Hom.: 2182 Cov.: 32 AF XY: 0.163 AC XY: 12108 AN XY: 74368

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.0838

Gnomad4 EAS AF: 0.370

Gnomad4 SAS AF: 0.210

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.150

Gnomad4 OTH AF: 0.137

Alfa AF: 0.146 Hom.: 2196

Bravo AF: 0.163

Asia WGS AF: 0.261 AC: 905 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.77

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: rs9384296; hg19: chr6-155530844;