NM_021649.7:c.603A>C

Variant names:

• chr5-115580654-T-G
• rs7705473
• NM_021649.7:c.603A>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BS1 BS2

The NM_021649.7(TICAM2):​c.603A>C​(p.Gly201Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00194 in 1,581,164 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.010 (28 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (23 hom.)
• Consequence: TICAM2 NM_021649.7 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.95
• Publications: 1 publications found

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]

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]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 5-115580654-T-G is Benign according to our data. Variant chr5-115580654-T-G is described in ClinVar as Benign. ClinVar VariationId is 790566.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.95 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0101 (1534/152270) while in subpopulation AFR AF = 0.0354 (1472/41534). AF 95% confidence interval is 0.0339. There are 28 homozygotes in GnomAd4. There are 709 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 28 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021649.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TICAM2	NM_021649.7	MANE Select	c.603A>C	p.Gly201Gly	synonymous	Exon 2 of 2	NP_067681.1	Q86XR7-1
	TMED7-TICAM2	NM_001164468.4		c.1110A>C	p.Gly370Gly	synonymous	Exon 4 of 4	NP_001157940.1
	TMED7-TICAM2	NM_001164469.4		c.*661A>C		3_prime_UTR	Exon 4 of 4	NP_001157941.1	A0A0A6YYA0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TICAM2	ENST00000427199.3	TSL:1 MANE Select	c.603A>C	p.Gly201Gly	synonymous	Exon 2 of 2	ENSP00000415139.3	Q86XR7-1
	TMED7-TICAM2	ENST00000282382.8	TSL:2	c.1110A>C	p.Gly370Gly	synonymous	Exon 4 of 4	ENSP00000282382.4
	TICAM2	ENST00000957908.1		c.603A>C	p.Gly201Gly	synonymous	Exon 2 of 2	ENSP00000627967.1

Frequencies

GnomAD3 genomes AF: 0.0101 AC: 1533 AN: 152152 Hom.: 28 Cov.: 32

Gnomad AFR AF: 0.0355

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00209

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

GnomAD2 exomes AF: 0.00306 AC: 657 AN: 214572 AF XY: 0.00235

Gnomad AFR exome AF: 0.0366

Gnomad AMR exome AF: 0.00211

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000190

Gnomad OTH exome AF: 0.000797

GnomAD4 exome AF: 0.00107 AC: 1536 AN: 1428894 Hom.: 23 Cov.: 31 AF XY: 0.000957 AC XY: 679 AN XY: 709522

African (AFR) AF: 0.0367 AC: 1159 AN: 31586

American (AMR) AF: 0.00194 AC: 71 AN: 36622

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23894

East Asian (EAS) AF: 0.00 AC: 0 AN: 39576

South Asian (SAS) AF: 0.0000754 AC: 6 AN: 79622

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52362

Middle Eastern (MID) AF: 0.00217 AC: 12 AN: 5532

European-Non Finnish (NFE) AF: 0.000125 AC: 138 AN: 1100818

Other (OTH) AF: 0.00255 AC: 150 AN: 58882

GnomAD4 genome AF: 0.0101 AC: 1534 AN: 152270 Hom.: 28 Cov.: 32 AF XY: 0.00952 AC XY: 709 AN XY: 74472

African (AFR) AF: 0.0354 AC: 1472 AN: 41534

American (AMR) AF: 0.00209 AC: 32 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68018

Other (OTH) AF: 0.00710 AC: 15 AN: 2114

Alfa AF: 0.00659 Hom.: 3

Bravo AF: 0.0114

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	9.3
DANN	Benign	0.71
PhyloP100		1.9
Mutation Taster		=100/0	polymorphism

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: rs7705473; hg19: chr5-114916351;