5-115581066-C-T

Position:

chr5-115581066-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_021649.7(TICAM2):c.191G>A(p.Ser64Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00191 in 1,614,192 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0098 ( 28 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 23 hom. )

Consequence

TICAM2
NM_021649.7 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.60

Variant links:

Genes affected

TICAM2 (HGNC:21354): (TIR domain containing adaptor molecule 2) Predicted to enable phospholipid binding activity. Involved in several processes, including TRAM-dependent toll-like receptor 4 signaling pathway; regulation of chemokine (C-C motif) ligand 5 production; and regulation of toll-like receptor 4 signaling pathway. Located in endoplasmic reticulum; endosome; and phagocytic cup. [provided by Alliance of Genome Resources, Apr 2022]

TICAM2 links:

TMED7-TICAM2 (HGNC:33945): (TMED7-TICAM2 readthrough) This locus represents naturally occurring read-through transcription between the neighboring transmembrane emp24 protein transport domain containing 7 (TMED7) and toll-like receptor adaptor molecule 2 (TICAM2) genes. Alternative splicing results in multiple transcript variants, one of which encodes a fusion protein that shares sequence identity with the products of each individual gene. This fusion product functions to negatively regulate the adaptor MyD88-independent toll-like receptor 4 pathway. [provided by RefSeq, Nov 2010]

TMED7-TICAM2 links:

TMED7-TICAM2 (HGNC:):

TMED7-TICAM2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025385022).

BP6

Variant 5-115581066-C-T is Benign according to our data. Variant chr5-115581066-C-T is described in ClinVar as [Benign]. Clinvar id is 790567.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00978 (1490/152312) while in subpopulation AFR AF= 0.0344 (1429/41556). AF 95% confidence interval is 0.0329. There are 28 homozygotes in gnomad4. There are 684 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 28 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TICAM2	NM_021649.7 linkuse as main transcript	c.191G>A	p.Ser64Asn	missense_variant	2/2	ENST00000427199.3	NP_067681.1	Q86XR7-1
TMED7-TICAM2	NM_001164468.4 linkuse as main transcript	c.698G>A	p.Ser233Asn	missense_variant	4/4		NP_001157940.1	Q86XR7-2
TMED7-TICAM2	NM_001164469.4 linkuse as main transcript	c.*249G>A		3_prime_UTR_variant	4/4		NP_001157941.1	Q86XR7Q9Y3B3-2A0A0A6YYA0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TICAM2	ENST00000427199.3 linkuse as main transcript	c.191G>A	p.Ser64Asn	missense_variant	2/2	1	NM_021649.7	ENSP00000415139.3	Q86XR7-1
TMED7-TICAM2	ENST00000282382.8 linkuse as main transcript	c.698G>A	p.Ser233Asn	missense_variant	4/4	2		ENSP00000282382.4
TMED7-TICAM2	ENST00000333314.3 linkuse as main transcript	c.*249G>A		3_prime_UTR_variant	4/4	2		ENSP00000333650.3	A0A0A6YYA0
TMED7-TICAM2	ENST00000514548.1 linkuse as main transcript	n.497G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.00980

AC:

1491

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0345

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00717

GnomAD3 exomes

AF:

0.00270

AC:

672

AN:

248888

Hom.:

AF XY:

0.00206

AC XY:

278

AN XY:

134722

show subpopulations

Gnomad AFR exome

AF:

0.0354

Gnomad AMR exome

AF:

0.00191

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000180

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.00109

AC:

1598

AN:

1461880

Hom.:

Cov.:

AF XY:

0.000971

AC XY:

706

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0359

Gnomad4 AMR exome

AF:

0.00195

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000927

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000126

Gnomad4 OTH exome

AF:

0.00245

GnomAD4 genome

AF:

0.00978

AC:

1490

AN:

152312

Hom.:

Cov.:

AF XY:

0.00918

AC XY:

684

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0344

Gnomad4 AMR

AF:

0.00203

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00129

Hom.:

Bravo

AF:

0.0110

ESP6500AA

AF:

0.0379

AC:

167

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00321

AC:

390

Asia WGS

AF:

0.00173

AC:

AN:

3476

EpiCase

AF:

0.000164

EpiControl

AF:

0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.095

DANN

Benign

0.92

DEOGEN2

Benign

0.087

.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.32

T;T

MetaRNN

Benign

0.0025

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

.;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.42

N;N

REVEL

Benign

0.038

Sift

Benign

0.14

T;T

Sift4G

Benign

0.23

T;T

Polyphen

0.0090

.;B

Vest4

0.049

MVP

0.055

MPC

0.79

ClinPred

0.0025

GERP RS

-0.31

Varity_R

0.044

gMVP

0.14

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over