rs2302592

Variant names:

• chr14-75662944-C-G
• rs2302592
• NM_015072.5:c.-95-111C>G

Variant summary

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

The NM_015072.5(TTLL5):​c.-95-111C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 660,392 control chromosomes in the GnomAD database, including 119,682 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 0.49 (22837 hom., cov: 32)
  • Exomes 𝑓: 0.61 (96845 hom.)
• Consequence: TTLL5 NM_015072.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0920
• Publications: 7 publications found

Genes affected

TTLL5 (HGNC:19963): (tubulin tyrosine ligase like 5) This gene encodes a member of the tubulin tyrosine ligase like protein family. This protein interacts with two glucocorticoid receptor coactivators, transcriptional intermediary factor 2 and steroid receptor coactivator 1. This protein may function as a coregulator of glucocorticoid receptor mediated gene induction and repression. This protein may also function as an alpha tubulin polyglutamylase.[provided by RefSeq, Feb 2010]

FLVCR2 (HGNC:20105): (FLVCR choline and putative heme transporter 2) This gene encodes a member of the major facilitator superfamily. The encoded transmembrane protein is a calcium transporter. Unlike the related protein feline leukemia virus subgroup C receptor 1, the protein encoded by this locus does not bind to feline leukemia virus subgroup C envelope protein. The encoded protein may play a role in development of brain vascular endothelial cells, as mutations at this locus have been associated with proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome. Alternatively spliced transcript variants have been described.[provided by RefSeq, Aug 2010]

FLVCR2 Gene-Disease associations (from GenCC):

• Fowler syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Laboratory for Molecular Medicine, G2P, Ambry Genetics, Genomics England PanelApp

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015072.5. 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
	TTLL5	NM_015072.5	MANE Select	c.-95-111C>G		intron	N/A	NP_055887.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTLL5	ENST00000298832.14	TSL:1 MANE Select	c.-95-111C>G		intron	N/A	ENSP00000298832.9	Q6EMB2-1
	TTLL5	ENST00000557636.5	TSL:1	c.-95-111C>G		intron	N/A	ENSP00000450713.1	G3V2J9
	TTLL5	ENST00000556977.5	TSL:1	c.-95-111C>G		intron	N/A	ENSP00000451917.1	Q2TAY9

Frequencies

GnomAD3 genomes AF: 0.495 AC: 75240 AN: 151998 Hom.: 22835 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.720

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.527

Gnomad FIN AF: 0.752

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.657

Gnomad OTH AF: 0.518

GnomAD4 exome AF: 0.605 AC: 307514 AN: 508276 Hom.: 96845 AF XY: 0.603 AC XY: 163508 AN XY: 271334

African (AFR) AF: 0.131 AC: 1912 AN: 14544

American (AMR) AF: 0.628 AC: 19284 AN: 30698

Ashkenazi Jewish (ASJ) AF: 0.517 AC: 8962 AN: 17346

East Asian (EAS) AF: 0.408 AC: 12910 AN: 31632

South Asian (SAS) AF: 0.530 AC: 29771 AN: 56174

European-Finnish (FIN) AF: 0.744 AC: 23973 AN: 32224

Middle Eastern (MID) AF: 0.447 AC: 1722 AN: 3856

European-Non Finnish (NFE) AF: 0.657 AC: 192474 AN: 293064

Other (OTH) AF: 0.574 AC: 16506 AN: 28738

GnomAD4 genome AF: 0.495 AC: 75239 AN: 152116 Hom.: 22837 Cov.: 32 AF XY: 0.500 AC XY: 37203 AN XY: 74354

African (AFR) AF: 0.135 AC: 5585 AN: 41504

American (AMR) AF: 0.585 AC: 8946 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.517 AC: 1794 AN: 3472

East Asian (EAS) AF: 0.369 AC: 1909 AN: 5174

South Asian (SAS) AF: 0.528 AC: 2547 AN: 4824

European-Finnish (FIN) AF: 0.752 AC: 7943 AN: 10568

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.657 AC: 44643 AN: 67966

Other (OTH) AF: 0.513 AC: 1085 AN: 2116

Alfa AF: 0.576 Hom.: 3565

Bravo AF: 0.470

Asia WGS AF: 0.429 AC: 1491 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.5
DANN	Benign	0.69
PhyloP100		-0.092
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: rs2302592; hg19: chr14-76129287; COSMIC: COSV54030070; COSMIC: COSV54030070;