17-58087192-A-G

Position:

• chr17-58087192-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_080677.3(DYNLL2):​c.102A>G​(p.Ile34Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DYNLL2 NM_080677.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.851

Genes affected

DYNLL2 (HGNC:24596): (dynein light chain LC8-type 2) Predicted to enable dynein intermediate chain binding activity and dynein light intermediate chain binding activity. Predicted to be involved in cilium assembly. Located in 9+0 non-motile cilium and centrosome. Is active in glutamatergic synapse and postsynapse. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DYNLL2	NM_080677.3	c.102A>G	p.Ile34Met	missense_variant	2/3	ENST00000579991.3	NP_542408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DYNLL2	ENST00000579991.3	c.102A>G	p.Ile34Met	missense_variant	2/3	1	NM_080677.3	ENSP00000477310.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 05, 2024

The c.102A>G (p.I34M) alteration is located in exon 2 (coding exon 1) of the DYNLL2 gene. This alteration results from a A to G substitution at nucleotide position 102, causing the isoleucine (I) at amino acid position 34 to be replaced by a methionine (M). 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	Uncertain	0.46
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Benign	23
DANN	Benign	0.96
DEOGEN2	Benign	0.086	T
Eigen	Benign	-0.017
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-0.92	T
PrimateAI	Pathogenic	0.81	D
Sift4G	Benign	0.24	T
Polyphen		0.15	B
Vest4		0.73
MutPred		0.47		Gain of disorder (P = 0.0307);
MVP		0.74
MPC		1.4
ClinPred		0.93	D
GERP RS		5.7
Varity_R		0.76
gMVP		0.80

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-56164553;