3-196317854-C-T

Variant names:

• chr3-196317854-C-T
• rs113961658
• NM_152773.5:c.113+186G>A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_152773.5(DYNLT2B):​c.113+186G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0761 in 152,082 control chromosomes in the GnomAD database, including 495 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.076 (495 hom., cov: 31)
• Consequence: DYNLT2B NM_152773.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0120

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]

ENSG00000272741 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 3-196317854-C-T is Benign according to our data. Variant chr3-196317854-C-T is described in ClinVar as [Benign]. Clinvar id is 1232495.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.094 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYNLT2B	NM_152773.5	c.113+186G>A		intron_variant	Intron 1 of 4	ENST00000325318.10	NP_689986.2
DYNLT2B	NM_001351628.2	c.113+186G>A		intron_variant	Intron 1 of 4		NP_001338557.1
TM4SF19-DYNLT2B	NR_037950.1	n.862-1623G>A		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DYNLT2B	ENST00000325318.10	c.113+186G>A		intron_variant	Intron 1 of 4	1	NM_152773.5	ENSP00000324323.5
ENSG00000272741	ENST00000431391.1	n.113+186G>A		intron_variant	Intron 1 of 5	5		ENSP00000405181.1
TM4SF19-DYNLT2B	ENST00000442633.1	n.*74-1623G>A		intron_variant	Intron 5 of 5	1		ENSP00000405973.1

Frequencies

GnomAD3 genomes AF: 0.0762 AC: 11576 AN: 151968 Hom.: 496 Cov.: 31

Gnomad AFR AF: 0.0565

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.0777

Gnomad ASJ AF: 0.0816

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0275

Gnomad FIN AF: 0.0721

Gnomad MID AF: 0.140

Gnomad NFE AF: 0.0960

Gnomad OTH AF: 0.0845

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0761 AC: 11575 AN: 152082 Hom.: 495 Cov.: 31 AF XY: 0.0730 AC XY: 5425 AN XY: 74366

Gnomad4 AFR AF: 0.0564

Gnomad4 AMR AF: 0.0776

Gnomad4 ASJ AF: 0.0816

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.0273

Gnomad4 FIN AF: 0.0721

Gnomad4 NFE AF: 0.0960

Gnomad4 OTH AF: 0.0827

Alfa AF: 0.0814 Hom.: 62

Bravo AF: 0.0784

Asia WGS AF: 0.0200 AC: 68 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 15, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.1
DANN	Benign	0.93
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

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

LitVar

Other links and lift over

dbSNP: rs113961658; hg19: chr3-196044725;