3-196296136-C-T

Variant names:

• chr3-196296136-C-T
• rs73212151
• NM_152773.5:c.318-67G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_152773.5(DYNLT2B):​c.318-67G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0654 in 1,323,530 control chromosomes in the GnomAD database, including 3,369 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.065 (380 hom., cov: 32)
  • Exomes 𝑓: 0.065 (2989 hom.)
• Consequence: DYNLT2B NM_152773.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.37
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• short-rib thoracic dysplasia 17 with or without polydactyly

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia

ENSG00000272741 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 3-196296136-C-T is Benign according to our data. Variant chr3-196296136-C-T is described in ClinVar as Benign. ClinVar VariationId is 1262426.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYNLT2B	NM_152773.5	MANE Select	c.318-67G>A		intron	N/A	NP_689986.2	Q8WW35
	DYNLT2B	NM_001351628.2		c.318-67G>A		intron	N/A	NP_001338557.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYNLT2B	ENST00000325318.10	TSL:1 MANE Select	c.318-67G>A		intron	N/A	ENSP00000324323.5	Q8WW35
	ENSG00000272741	ENST00000431391.1	TSL:5	n.317+10807G>A		intron	N/A	ENSP00000405181.1	E7ESA3
	DYNLT2B	ENST00000931284.1		c.492-67G>A		intron	N/A	ENSP00000601343.1

Frequencies

GnomAD3 genomes AF: 0.0654 AC: 9956 AN: 152134 Hom.: 379 Cov.: 32

Gnomad AFR AF: 0.0760

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.0447

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.0169

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.0372

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0648

Gnomad OTH AF: 0.0611

GnomAD4 exome AF: 0.0653 AC: 76540 AN: 1171278 Hom.: 2989 Cov.: 16 AF XY: 0.0682 AC XY: 40655 AN XY: 596286

African (AFR) AF: 0.0746 AC: 2057 AN: 27578

American (AMR) AF: 0.0336 AC: 1471 AN: 43756

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 2709 AN: 24184

East Asian (EAS) AF: 0.0170 AC: 650 AN: 38248

South Asian (SAS) AF: 0.121 AC: 9657 AN: 79844

European-Finnish (FIN) AF: 0.0404 AC: 2142 AN: 53052

Middle Eastern (MID) AF: 0.124 AC: 645 AN: 5194

European-Non Finnish (NFE) AF: 0.0630 AC: 53495 AN: 848668

Other (OTH) AF: 0.0732 AC: 3714 AN: 50754

GnomAD4 genome AF: 0.0654 AC: 9960 AN: 152252 Hom.: 380 Cov.: 32 AF XY: 0.0659 AC XY: 4902 AN XY: 74434

African (AFR) AF: 0.0760 AC: 3156 AN: 41548

American (AMR) AF: 0.0446 AC: 682 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 387 AN: 3470

East Asian (EAS) AF: 0.0167 AC: 87 AN: 5196

South Asian (SAS) AF: 0.123 AC: 594 AN: 4818

European-Finnish (FIN) AF: 0.0372 AC: 394 AN: 10594

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0648 AC: 4406 AN: 68012

Other (OTH) AF: 0.0605 AC: 128 AN: 2116

Alfa AF: 0.0680 Hom.: 99

Bravo AF: 0.0652

Asia WGS AF: 0.0620 AC: 217 AN: 3478

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_noAF	Benign	-0.96
CADD	Benign	0.024
DANN	Benign	0.57
PhyloP100		-1.4
Mutation Taster		=100/0	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: rs73212151; hg19: chr3-196023007;