chr3-196318107-G-A

Position:

chr3-196318107-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_152773.5(DYNLT2B):c.46C>T(p.Pro16Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,397,440 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 29)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DYNLT2B
NM_152773.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.493

Variant links:

Genes affected

DYNLT2B (HGNC:28482): (dynein light chain Tctex-type 2B) Dyneins are a group of microtubule-activated ATPases that function as molecular motors. They are divided into two subgroups of axonemal and cytoplasmic dyneins. The cytoplasmic dyneins function in intracellular motility, including retrograde axonal transport, protein sorting, organelle movement, and spindle dynamics. Molecules of conventional cytoplasmic dynein are comprised of 2 heavy chain polypeptides and a number of intermediate and light chains. This gene encodes a subunit of the human cytoplasmic dynein-2 complex. Mutations in this gene are associated with short-rib thoracic dysplasia 17 with or without polydactyly. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2017]

DYNLT2B links:

TM4SF19-DYNLT2B (HGNC:):

TM4SF19-DYNLT2B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.044897348).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
DYNLT2B	NM_152773.5 linkuse as main transcript	c.46C>T	p.Pro16Ser	missense_variant	1/5	ENST00000325318.10
TM4SF19-DYNLT2B	NR_037950.1 linkuse as main transcript	n.862-1876C>T		intron_variant, non_coding_transcript_variant
DYNLT2B	NM_001351628.2 linkuse as main transcript	c.46C>T	p.Pro16Ser	missense_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
DYNLT2B	ENST00000325318.10 linkuse as main transcript	c.46C>T	p.Pro16Ser	missense_variant	1/5	1	NM_152773.5	P1
DYNLT2B	ENST00000446494.1 linkuse as main transcript	c.46C>T	p.Pro16Ser	missense_variant, NMD_transcript_variant	1/6	3
DYNLT2B	ENST00000426563.5 linkuse as main transcript	c.46C>T	p.Pro16Ser	missense_variant, NMD_transcript_variant	1/5	2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

114604

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000143

AC:

AN:

1397440

Hom.:

Cov.:

AF XY:

0.00000144

AC XY:

AN XY:

694700

show subpopulations

Gnomad4 AFR exome

AF:

0.0000342

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000300

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000262

AC:

AN:

114604

Hom.:

Cov.:

AF XY:

0.0000363

AC XY:

AN XY:

55102

show subpopulations

Gnomad4 AFR

AF:

0.000101

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000825

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 09, 2024

The c.46C>T (p.P16S) alteration is located in exon 1 (coding exon 1) of the TCTEX1D2 gene. This alteration results from a C to T substitution at nucleotide position 46, causing the proline (P) at amino acid position 16 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

0.079

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.1

DANN

Benign

0.77

DEOGEN2

Benign

0.0042

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.37

M_CAP

Benign

0.027

MetaRNN

Benign

0.045

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.10

REVEL

Benign

0.073

Sift

Benign

0.43

Sift4G

Benign

0.66

Polyphen

0.0

Vest4

0.075

MutPred

0.40

Gain of helix (P = 0.0128);

MVP

0.014

MPC

0.38

ClinPred

0.018

GERP RS

-2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.027

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over