6-155159091-T-C

Variant names:

• chr6-155159091-T-C
• rs1385732
• NM_012454.4:c.2029-5324T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012454.4(TIAM2):​c.2029-5324T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 152,002 control chromosomes in the GnomAD database, including 17,366 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 0.47 (17366 hom., cov: 32)
• Consequence: TIAM2 NM_012454.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0670
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TIAM2	NM_012454.4	c.2029-5324T>C		intron_variant	Intron 7 of 26	ENST00000682666.1	NP_036586.3
TIAM2	NM_001384546.1	c.2029-5324T>C		intron_variant	Intron 7 of 26		NP_001371475.1
TIAM2	NM_001384547.1	c.2029-5324T>C		intron_variant	Intron 6 of 25		NP_001371476.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TIAM2	ENST00000682666.1	c.2029-5324T>C		intron_variant	Intron 7 of 26		NM_012454.4	ENSP00000507157.1

Frequencies

GnomAD3 genomes AF: 0.471 AC: 71578 AN: 151884 Hom.: 17357 Cov.: 32

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.542

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.581

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.528

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.503

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

GnomAD4 genome AF: 0.471 AC: 71601 AN: 152002 Hom.: 17366 Cov.: 32 AF XY: 0.473 AC XY: 35103 AN XY: 74268

African (AFR) AF: 0.347 AC: 14371 AN: 41448

American (AMR) AF: 0.536 AC: 8184 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.581 AC: 2015 AN: 3468

East Asian (EAS) AF: 0.549 AC: 2838 AN: 5174

South Asian (SAS) AF: 0.528 AC: 2543 AN: 4812

European-Finnish (FIN) AF: 0.492 AC: 5183 AN: 10542

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.511 AC: 34754 AN: 67960

Other (OTH) AF: 0.500 AC: 1057 AN: 2112

Alfa AF: 0.486 Hom.: 2374

Bravo AF: 0.472

Asia WGS AF: 0.491 AC: 1707 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	5.4
DANN	Benign	0.74
PhyloP100		-0.067
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1385732; hg19: chr6-155480225; COSMIC: COSV59702796;