chr14-21032059-C-G

Variant names:

• chr14-21032059-C-G
• rs76101114
• NM_173846.5:c.495C>G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_173846.5(TPPP2):​c.495C>G​(p.Tyr165*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00497 in 1,613,678 control chromosomes in the GnomAD database, including 251 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (115 hom., cov: 32)
  • Exomes 𝑓: 0.0031 (136 hom.)
• Consequence: TPPP2 NM_173846.5 stop_gained
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.220
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 14-21032059-C-G is Benign according to our data. Variant chr14-21032059-C-G is described in ClinVar as Benign. ClinVar VariationId is 776817.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0739 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173846.5. 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
	TPPP2	NM_173846.5	MANE Select	c.495C>G	p.Tyr165*	stop_gained	Exon 4 of 4	NP_776245.2	P59282
	NDRG2	NM_001282211.2		c.25-8738G>C		intron	N/A	NP_001269140.1	Q9UN36-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPPP2	ENST00000321760.11	TSL:1 MANE Select	c.495C>G	p.Tyr165*	stop_gained	Exon 4 of 4	ENSP00000317595.6	P59282
	TPPP2	ENST00000534434.2	TSL:1	n.940C>G		non_coding_transcript_exon	Exon 3 of 3
	TPPP2	ENST00000530140.6	TSL:2	c.495C>G	p.Tyr165*	stop_gained	Exon 4 of 4	ENSP00000435356.2	P59282

Frequencies

GnomAD3 genomes AF: 0.0228 AC: 3467 AN: 152098 Hom.: 115 Cov.: 32

Gnomad AFR AF: 0.0759

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00944

Gnomad ASJ AF: 0.0276

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000632

Gnomad OTH AF: 0.0167

GnomAD2 exomes AF: 0.00724 AC: 1817 AN: 251076 AF XY: 0.00579

Gnomad AFR exome AF: 0.0764

Gnomad AMR exome AF: 0.00448

Gnomad ASJ exome AF: 0.0307

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000608

Gnomad OTH exome AF: 0.00637

GnomAD4 exome AF: 0.00310 AC: 4534 AN: 1461462 Hom.: 136 Cov.: 31 AF XY: 0.00282 AC XY: 2051 AN XY: 726954

African (AFR) AF: 0.0796 AC: 2663 AN: 33472

American (AMR) AF: 0.00532 AC: 238 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.0299 AC: 781 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.000209 AC: 18 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00625 AC: 36 AN: 5760

European-Non Finnish (NFE) AF: 0.000299 AC: 332 AN: 1111686

Other (OTH) AF: 0.00772 AC: 466 AN: 60370

GnomAD4 genome AF: 0.0229 AC: 3482 AN: 152216 Hom.: 115 Cov.: 32 AF XY: 0.0221 AC XY: 1647 AN XY: 74416

African (AFR) AF: 0.0761 AC: 3158 AN: 41506

American (AMR) AF: 0.00943 AC: 144 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0276 AC: 96 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000830 AC: 4 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

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

European-Non Finnish (NFE) AF: 0.000632 AC: 43 AN: 68028

Other (OTH) AF: 0.0166 AC: 35 AN: 2112

Alfa AF: 0.00371 Hom.: 5

Bravo AF: 0.0257

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.0756 AC: 333

ESP6500EA AF: 0.00151 AC: 13

ExAC AF: 0.00795 AC: 965

Asia WGS AF: 0.00549 AC: 19 AN: 3478

EpiCase AF: 0.00109

EpiControl AF: 0.000948

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Pathogenic	0.59
CADD	Pathogenic	36
DANN	Uncertain	1.0
Eigen	Uncertain	0.34
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.82	D
PhyloP100		0.22
Vest4		0.26
GERP RS		3.6
Mutation Taster		=148/52	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs76101114; hg19: chr14-21500218;