rs12523857

chr6-155066105-T-Achr6-155066105-T-Cchr6-155066105-T-G

Variant summary

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

The NM_012454.4(TIAM2):c.-208-24184T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 151,862 control chromosomes in the GnomAD database, including 10,527 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 0.36 (10527 hom., cov: 32)
• Consequence: TIAM2 NM_012454.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.225

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TIAM2	NM_012454.4	c.-208-24184T>A		intron_variant		ENST00000682666.1
TIAM2	NM_001384546.1	c.-208-24184T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TIAM2	ENST00000682666.1	c.-208-24184T>A		intron_variant			NM_012454.4	A2

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54248 AN: 151744 Hom.: 10527 Cov.: 32

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.381

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

GnomAD4 genome AF: 0.357 AC: 54261 AN: 151862 Hom.: 10527 Cov.: 32 AF XY: 0.354 AC XY: 26279 AN XY: 74206

Gnomad4 AFR AF: 0.208

Gnomad4 AMR AF: 0.312

Gnomad4 ASJ AF: 0.441

Gnomad4 EAS AF: 0.357

Gnomad4 SAS AF: 0.437

Gnomad4 FIN AF: 0.382

Gnomad4 NFE AF: 0.445

Gnomad4 OTH AF: 0.380

Alfa AF: 0.265 Hom.: 698

Bravo AF: 0.344

Asia WGS AF: 0.361 AC: 1254 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.0
Dann	Benign	0.73

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: rs12523857; hg19: chr6-155387239;