Genetic Variant DYNLT2B:c.113+10G>A (chr3-196318030-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_152773.5(DYNLT2B):c.113+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000819 in 1,343,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

DYNLT2B
NM_152773.5 intron

Scores

Splicing: ADA: 0.0006283

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.838

Publications

0 publications found

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:

ENSG00000272741 (HGNC:):

ENSG00000272741 links:

TM4SF19-DYNLT2B (HGNC:49190): (TM4SF19-DYNLT2B readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring transmembrane 4 L six family member 19 (TM4SF19) and Tctex1 domain containing 2 (TCTEX1D2) genes on chromosome 3. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus not expected to produce a protein product. [provided by RefSeq, Mar 2011]

TM4SF19-DYNLT2B links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152773.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DYNLT2B	NM_152773.5	MANE Select	c.113+10G>A	intron	N/A	NP_689986.2	Q8WW35
DYNLT2B	NM_001351628.2		c.113+10G>A	intron	N/A	NP_001338557.1
TM4SF19-DYNLT2B	NR_037950.1		n.862-1799G>A	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DYNLT2B	ENST00000325318.10	TSL:1 MANE Select	c.113+10G>A	intron	N/A	ENSP00000324323.5	Q8WW35
ENSG00000272741	ENST00000431391.1	TSL:5	n.113+10G>A	intron	N/A	ENSP00000405181.1	E7ESA3
TM4SF19-DYNLT2B	ENST00000442633.1	TSL:1	n.*74-1799G>A	intron	N/A	ENSP00000405973.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000138

AC:

AN:

144994

AF XY:

0.0000125

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000819

AC:

AN:

1343870

Hom.:

Cov.:

AF XY:

0.00000901

AC XY:

AN XY:

665818

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28410

American (AMR)

AF:

0.00

AC:

AN:

28320

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23116

East Asian (EAS)

AF:

0.00

AC:

AN:

30980

South Asian (SAS)

AF:

0.000137

AC:

AN:

72804

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47146

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5426

European-Non Finnish (NFE)

AF:

9.50e-7

AC:

AN:

1052404

Other (OTH)

AF:

0.00

AC:

AN:

55264

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

7.1

(source)

DANN

Benign

0.91

PhyloP100

-0.84

PromoterAI

-0.093

Neutral

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00063

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over