chr17-64160922-C-T

Position:

• chr17-64160922-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001288732.2(TEX2):​c.2683G>A​(p.Asp895Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TEX2 NM_001288732.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.15

Genes affected

TEX2 (HGNC:30884): (testis expressed 2) Predicted to enable lipid binding activity. Predicted to be involved in lipid transport. Predicted to be located in endoplasmic reticulum membrane and nuclear membrane. Predicted to be integral component of membrane. Predicted to be active in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TEX2	NM_001288732.2	c.2683G>A	p.Asp895Asn	missense_variant	8/12	ENST00000584379.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TEX2	ENST00000584379.6	c.2683G>A	p.Asp895Asn	missense_variant	8/12	1	NM_001288732.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000205 AC: 3 AN: 1461766 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727192

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: 8.99e-7

Gnomad4 OTH exome AF: 0.0000331

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2024

The c.2704G>A (p.D902N) alteration is located in exon 8 (coding exon 7) of the TEX2 gene. This alteration results from a G to A substitution at nucleotide position 2704, causing the aspartic acid (D) at amino acid position 902 to be replaced by an asparagine (N). 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	Uncertain	0.53
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.37
CADD	Pathogenic	27
DANN	Uncertain	0.99
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.91	D;.;D;D
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.71	D;D;D;D
MetaSVM	Benign	-0.46	T
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-3.5	D;.;.;.
REVEL	Benign	0.26
Sift	Benign	0.099	T;.;.;.
Sift4G	Uncertain	0.030	D;D;D;D
Polyphen		0.98	D;D;.;D
Vest4		0.66
MutPred		0.65		.;Loss of sheet (P = 0.302);Loss of sheet (P = 0.302);Loss of sheet (P = 0.302);
MVP		0.53
MPC		0.59
ClinPred		0.98	D
GERP RS		3.9
Varity_R		0.22
gMVP		0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr17-62238282;