chr2-195754381-T-C

Position:

• chr2-195754381-T-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_018897.3(DNAH7):​c.11720A>G​(p.Tyr3907Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00686 in 1,614,006 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0048 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0071 (56 hom.)
• Consequence: DNAH7 NM_018897.3 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 3.41

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]

LOC107985972 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.01423794).
• BP6: Variant 2-195754381-T-C is Benign according to our data. Variant chr2-195754381-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 718311.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 56 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH7	NM_018897.3	c.11720A>G	p.Tyr3907Cys	missense_variant	63/65	ENST00000312428.11
LOC107985972	XR_001739837.2	n.1828-3719T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH7	ENST00000312428.11	c.11720A>G	p.Tyr3907Cys	missense_variant	63/65	1	NM_018897.3	P1
DNAH7	ENST00000409063.5	c.1169A>G	p.Tyr390Cys	missense_variant	8/10	1
DNAH7	ENST00000438565.1	c.66+1752A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.00483 AC: 735 AN: 152110 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00181

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00518

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.000753

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00797

Gnomad OTH AF: 0.00480

GnomAD3 exomes AF: 0.00457 AC: 1139 AN: 249328 Hom.: 10 AF XY: 0.00472 AC XY: 638 AN XY: 135280

Gnomad AFR exome AF: 0.00116

Gnomad AMR exome AF: 0.00345

Gnomad ASJ exome AF: 0.00596

Gnomad EAS exome AF: 0.000111

Gnomad SAS exome AF: 0.00124

Gnomad FIN exome AF: 0.000464

Gnomad NFE exome AF: 0.00768

Gnomad OTH exome AF: 0.00380

GnomAD4 exome AF: 0.00708 AC: 10345 AN: 1461778 Hom.: 56 Cov.: 31 AF XY: 0.00701 AC XY: 5100 AN XY: 727192

Gnomad4 AFR exome AF: 0.000926

Gnomad4 AMR exome AF: 0.00347

Gnomad4 ASJ exome AF: 0.00559

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00121

Gnomad4 FIN exome AF: 0.000842

Gnomad4 NFE exome AF: 0.00856

Gnomad4 OTH exome AF: 0.00543

GnomAD4 genome AF: 0.00483 AC: 735 AN: 152228 Hom.: 1 Cov.: 32 AF XY: 0.00455 AC XY: 339 AN XY: 74424

Gnomad4 AFR AF: 0.00181

Gnomad4 AMR AF: 0.00517

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.000753

Gnomad4 NFE AF: 0.00797

Gnomad4 OTH AF: 0.00475

Alfa AF: 0.00782 Hom.: 10

Bravo AF: 0.00506

TwinsUK AF: 0.00944 AC: 35

ALSPAC AF: 0.00571 AC: 22

ESP6500AA AF: 0.00104 AC: 4

ESP6500EA AF: 0.00836 AC: 69

ExAC AF: 0.00465 AC: 562

EpiCase AF: 0.00867

EpiControl AF: 0.00670

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2024	DNAH7: BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

DNAH7-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 13, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.046	.;T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.014	T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.2	.;L
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.67	T
PROVEAN	Pathogenic	-6.8	D;D
REVEL	Benign	0.15
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.019	D;.
Polyphen		1.0	.;D
Vest4		0.69
MVP		0.50
MPC		0.24
ClinPred		0.052	T
GERP RS		5.5
Varity_R		0.57
gMVP		0.74

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: rs78583300; hg19: chr2-196619105;