Genetic Variant NM_018897.3:c.1139T>C (chr2-196001709-A-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_018897.3(DNAH7):c.1139T>C(p.Met380Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000694 in 1,440,414 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. M380R) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

DNAH7
NM_018897.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.14

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:

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ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
DNAH7	NM_018897.3 link	c.1139T>C	p.Met380Thr	missense_variant	Exon 11 of 65	ENST00000312428.11	NP_061720.2	Q8WXX0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH7	ENST00000312428.11 link	c.1139T>C	p.Met380Thr	missense_variant	Exon 11 of 65	1	NM_018897.3	ENSP00000311273.6		Q8WXX0-1
DNAH7	ENST00000410072.5 link	c.1139T>C	p.Met380Thr	missense_variant	Exon 11 of 13	2		ENSP00000386260.1		Q8WXX0-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.94e-7

AC:

AN:

1440414

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

715016

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.07e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.81

BayesDel_addAF

Uncertain

0.045

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.049

T;.

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.78

T;T

M_CAP

Benign

0.0084

MetaRNN

Uncertain

0.66

D;D

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

M;M

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-3.4

D;D

REVEL

Benign

0.21

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.011

.;D

Polyphen

0.35

B;.

Vest4

0.66

MutPred

0.66

Loss of stability (P = 0.0441);Loss of stability (P = 0.0441);

MVP

0.26

MPC

0.037

ClinPred

0.98

GERP RS

5.7

Varity_R

0.72

gMVP

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Computational scores

Splicing

Publications

Other links and lift over