Variant 2-195738085-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018897.3(DNAH7):c.11911C>T(p.Pro3971Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,614 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

DNAH7
NM_018897.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.06

Variant links:

Genes affected

DNAH7 (HGNC:18661): (dynein axonemal heavy chain 7) DNAH7 is a component of the inner dynein arm of ciliary axonemes (Zhang et al., 2002 [PubMed 11877439]).[supplied by OMIM, Mar 2008]

DNAH7 links:

LOC107985972 (HGNC:):

LOC107985972 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.18105775).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH7	NM_018897.3 linkuse as main transcript	c.11911C>T	p.Pro3971Ser	missense_variant	65/65	ENST00000312428.11	NP_061720.2
LOC107985972	XR_001739837.2 linkuse as main transcript			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH7	ENST00000312428.11 linkuse as main transcript	c.11911C>T	p.Pro3971Ser	missense_variant	65/65	1	NM_018897.3	ENSP00000311273	P1	Q8WXX0-1
DNAH7	ENST00000409063.5 linkuse as main transcript	c.1360C>T	p.Pro454Ser	missense_variant	10/10	1		ENSP00000386912		Q8WXX0-2
DNAH7	ENST00000438565.1 linkuse as main transcript	c.*42C>T		3_prime_UTR_variant	3/3	3		ENSP00000409732
DNAH7	ENST00000484183.1 linkuse as main transcript	n.409C>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461614

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727124

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 30, 2021

The c.11911C>T (p.P3971S) alteration is located in exon 65 (coding exon 65) of the DNAH7 gene. This alteration results from a C to T substitution at nucleotide position 11911, causing the proline (P) at amino acid position 3971 to be replaced by a serine (S). 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

Benign

0.088

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.61

DEOGEN2

Benign

0.012

.;T

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.62

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.15

T;T

M_CAP

Benign

0.0040

MetaRNN

Benign

0.18

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.75

.;N

MutationTaster

Benign

0.71

D;D

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-3.9

D;N

REVEL

Benign

0.10

Sift

Benign

0.64

T;T

Sift4G

Benign

0.69

T;.

Polyphen

0.39

.;B

Vest4

0.25

MutPred

0.32

.;Gain of phosphorylation at P3971 (P = 0.0293);

MVP

0.13

MPC

0.031

ClinPred

0.29

GERP RS

2.7

Varity_R

0.055

gMVP

0.35

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over