Variant 2-195754442-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_018897.3(DNAH7):c.11659G>A(p.Gly3887Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000242 in 1,613,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

DNAH7
NM_018897.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.89

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.35250127).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH7	NM_018897.3 linkuse as main transcript	c.11659G>A	p.Gly3887Ser	missense_variant	63/65	ENST00000312428.11	NP_061720.2
LOC107985972	XR_001739837.2 linkuse as main transcript	n.1828-3658C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH7	ENST00000312428.11 linkuse as main transcript	c.11659G>A	p.Gly3887Ser	missense_variant	63/65	1	NM_018897.3	ENSP00000311273	P1	Q8WXX0-1
DNAH7	ENST00000409063.5 linkuse as main transcript	c.1108G>A	p.Gly370Ser	missense_variant	8/10	1		ENSP00000386912		Q8WXX0-2
DNAH7	ENST00000438565.1 linkuse as main transcript	c.66+1691G>A		intron_variant		3		ENSP00000409732

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000802

AC:

AN:

249372

Hom.:

AF XY:

0.0000813

AC XY:

AN XY:

135288

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.000464

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000557

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000884

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000233

AC:

AN:

1461802

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

727194

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.000380

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000989

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152140

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000680

Hom.:

Bravo

AF:

0.0000529

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000993

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

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

Sep 16, 2021

The c.11659G>A (p.G3887S) alteration is located in exon 63 (coding exon 63) of the DNAH7 gene. This alteration results from a G to A substitution at nucleotide position 11659, causing the glycine (G) at amino acid position 3887 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

Pathogenic

0.75

BayesDel_addAF

Benign

-0.082

BayesDel_noAF

Uncertain

-0.030

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.047

.;T

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.94

D;D

M_CAP

Benign

0.025

MetaRNN

Benign

0.35

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.8

.;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.83

PROVEAN

Pathogenic

-6.0

D;D

REVEL

Benign

0.29

Sift

Uncertain

0.0050

D;D

Sift4G

Benign

0.091

T;.

Polyphen

0.93

.;P

Vest4

0.54

MVP

0.47

MPC

0.13

ClinPred

0.93

GERP RS

5.5

Varity_R

0.76

gMVP

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over