rs767894947

Variant names:

• chr14-21031035-C-A
• NM_173846.5:c.197C>A

Your query was ambiguous. Multiple possible variants found:

• chr14-21031035-C-A
• chr14-21031035-C-G
• chr14-21031035-C-T

Variant summary

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

The NM_173846.5(TPPP2):​c.197C>A​(p.Thr66Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,460,926 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: TPPP2 NM_173846.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.645

Genes affected

TPPP2 (HGNC:19293): (tubulin polymerization promoting protein family member 2) Enables tubulin binding activity. Involved in regulation of flagellated sperm motility. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

NDRG2 (HGNC:14460): (NDRG family member 2) This gene is a member of the N-myc downregulated gene family which belongs to the alpha/beta hydrolase superfamily. The protein encoded by this gene is a cytoplasmic protein that may play a role in neurite outgrowth. This gene may be involved in glioblastoma carcinogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2017]

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 rank	MANE	Protein	UniProt
TPPP2	NM_173846.5	c.197C>A	p.Thr66Lys	missense_variant	Exon 3 of 4	ENST00000321760.11	NP_776245.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPPP2	ENST00000321760.11	c.197C>A	p.Thr66Lys	missense_variant	Exon 3 of 4	1	NM_173846.5	ENSP00000317595.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000548 AC: 8 AN: 1460926 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4 AN XY: 726706

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000384

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Benign	-0.019	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.16	T;.;T;.;T
Eigen	Benign	0.15
Eigen_PC	Benign	0.065
FATHMM_MKL	Benign	0.66	D
LIST_S2	Uncertain	0.91	.;D;D;D;D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.44	T;T;T;T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Pathogenic	3.0	M;.;M;.;.
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-3.0	D;D;D;D;D
REVEL	Benign	0.26
Sift	Uncertain	0.025	D;D;D;D;D
Sift4G	Benign	0.11	T;D;T;D;D
Polyphen		0.92	P;.;P;.;.
Vest4		0.58
MutPred		0.65		Gain of methylation at T66 (P = 0.0044);Gain of methylation at T66 (P = 0.0044);Gain of methylation at T66 (P = 0.0044);Gain of methylation at T66 (P = 0.0044);.;
MVP		0.048
MPC		0.34
ClinPred		0.95	D
GERP RS		2.6
Varity_R		0.18
gMVP		0.64

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: chr14-21499194;