rs1858012761

Variant names:

• chr11-103109635-T-C
• rs1858012761
• NM_001080463.2:c.61T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-103109635-T-C
• chr11-103109635-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001377.3(DYNC2H1):​c.61T>C​(p.Phe21Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 32)
• Consequence: DYNC2H1 NM_001377.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.86

Genes affected

DYNC2H1 (HGNC:2962): (dynein cytoplasmic 2 heavy chain 1) This gene encodes a large cytoplasmic dynein protein that is involved in retrograde transport in the cilium and has a role in intraflagellar transport, a process required for ciliary/flagellar assembly. Mutations in this gene cause a heterogeneous spectrum of conditions related to altered primary cilium function and often involve polydactyly, abnormal skeletogenesis, and polycystic kidneys. Alternative splicing results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, Jan 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13746166).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYNC2H1	NM_001080463.2	c.61T>C	p.Phe21Leu	missense_variant	Exon 1 of 90	ENST00000650373.2	NP_001073932.1
DYNC2H1	NM_001377.3	c.61T>C	p.Phe21Leu	missense_variant	Exon 1 of 89	ENST00000375735.7	NP_001368.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DYNC2H1	ENST00000650373.2	c.61T>C	p.Phe21Leu	missense_variant	Exon 1 of 90		NM_001080463.2	ENSP00000497174.1
DYNC2H1	ENST00000375735.7	c.61T>C	p.Phe21Leu	missense_variant	Exon 1 of 89	1	NM_001377.3	ENSP00000364887.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	24
DANN	Benign	0.96
DEOGEN2	Benign	0.060	.;T;.;T;.;.
Eigen	Benign	-0.16
Eigen_PC	Benign	0.038
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.74	T;.;T;T;.;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.14	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	.;L;L;L;L;L
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.1	.;N;D;.;.;N
REVEL	Benign	0.042
Sift	Benign	0.26	.;T;T;.;.;T
Sift4G	Benign	1.0	.;T;T;.;.;T
Polyphen		0.0010, 0.0020	.;B;B;B;B;B
Vest4		0.28, 0.22, 0.28
MutPred		0.29		Gain of catalytic residue at F21 (P = 0.0555);Gain of catalytic residue at F21 (P = 0.0555);Gain of catalytic residue at F21 (P = 0.0555);Gain of catalytic residue at F21 (P = 0.0555);Gain of catalytic residue at F21 (P = 0.0555);Gain of catalytic residue at F21 (P = 0.0555);
MVP		0.51
MPC		0.072
ClinPred		0.56	D
GERP RS		4.5
Varity_R		0.23
gMVP		0.58

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: rs1858012761; hg19: chr11-102980364;