rs866607500

Variant names:

• chr2-84525598-C-G
• rs866607500
• NM_001370.2:c.259C>G

Your query was ambiguous. Multiple possible variants found:

• chr2-84525598-C-G
• chr2-84525598-C-T

Variant summary

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

The NM_001370.2(DNAH6):​c.259C>G​(p.Pro87Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P87S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNAH6 NM_001370.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.17

Genes affected

DNAH6 (HGNC:2951): (dynein axonemal heavy chain 6) This gene belongs to the dynein family, whose members encode large proteins that are constituents of the microtubule-associated motor protein complex. This complex is composed of dynein heavy, intermediate and light chains, which can be axonemal or cytoplasmic. This protein is an axonemal dynein heavy chain. It is involved in producing force for ciliary beating by using energy from ATP hydrolysis. Mutations in this gene may cause primary ciliary dyskinesia (PCD) as well as heterotaxy. [provided by RefSeq, Jun 2016]

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=0.14712414).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH6	NM_001370.2	c.259C>G	p.Pro87Ala	missense_variant	Exon 3 of 77	ENST00000389394.8	NP_001361.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH6	ENST00000389394.8	c.259C>G	p.Pro87Ala	missense_variant	Exon 3 of 77	5	NM_001370.2	ENSP00000374045.3
DNAH6	ENST00000494025.1	n.229+7547C>G		intron_variant	Intron 1 of 8	1
DNAH6	ENST00000468661.1	n.314C>G		non_coding_transcript_exon_variant	Exon 3 of 4	4
DNAH6	ENST00000476689.5	n.396C>G		non_coding_transcript_exon_variant	Exon 3 of 11	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.017	T;T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.0064
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.75	T;.
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;L
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.6	D;D
REVEL	Benign	0.052
Sift	Benign	0.048	D;D
Polyphen		0.15	B;B
Vest4		0.32
MutPred		0.52		Gain of helix (P = 0.005);Gain of helix (P = 0.005);
MVP		0.29
MPC		0.12
ClinPred		0.44	T
GERP RS		4.7
Varity_R		0.11
gMVP		0.29

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: rs866607500; hg19: chr2-84752722;