NM_001164407.2:c.202G>T

Variant names:

• chr17-1709861-C-A
• NM_001164407.2:c.202G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001164407.2(TLCD2):​c.202G>T​(p.Ala68Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TLCD2 NM_001164407.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.37

Genes affected

TLCD2 (HGNC:33522): (TLC domain containing 2) Involved in several processes, including membrane assembly; phospholipid homeostasis; and regulation of membrane lipid distribution. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.039324522).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLCD2	NM_001164407.2	c.202G>T	p.Ala68Ser	missense_variant	Exon 2 of 4	ENST00000330676.8	NP_001157879.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLCD2	ENST00000330676.8	c.202G>T	p.Ala68Ser	missense_variant	Exon 2 of 4	2	NM_001164407.2	ENSP00000331965.6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1374686 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 678662

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.202G>T (p.A68S) alteration is located in exon 2 (coding exon 2) of the TLCD2 gene. This alteration results from a G to T substitution at nucleotide position 202, causing the alanine (A) at amino acid position 68 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	4.2
DANN	Benign	0.69
DEOGEN2	Benign	0.18	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.047	N
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.23	N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.83	N
REVEL	Benign	0.16
Sift	Benign	0.69	T
Sift4G	Benign	0.72	T
Vest4		0.090
MutPred		0.30		Gain of glycosylation at A68 (P = 0.0138);
MVP		0.11
ClinPred		0.048	T
GERP RS		-12
Varity_R		0.041
gMVP		0.10

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-1613155;