2-195891811-GAAA-GA

Variant names:

• chr2-195891811-GAA-G
• rs11292337
• NM_018897.3:c.4897-9_4897-8delTT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_018897.3(DNAH7):​c.4897-9_4897-8delTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 1,223,982 control chromosomes in the GnomAD database, including 5,971 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.099 (843 hom., cov: 0)
  • Exomes 𝑓: 0.11 (5128 hom.)
• Consequence: DNAH7 NM_018897.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.10
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• ciliary dyskinesia, primary, 50

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AR Classification: LIMITED Submitted by: King Faisal Specialist Hospital and Research Center

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH7	NM_018897.3	c.4897-9_4897-8delTT		splice_region_variant, intron_variant	Intron 30 of 64	ENST00000312428.11	NP_061720.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH7	ENST00000312428.11	c.4897-9_4897-8delTT		splice_region_variant, intron_variant	Intron 30 of 64	1	NM_018897.3	ENSP00000311273.6

Frequencies

GnomAD3 genomes AF: 0.0985 AC: 14736 AN: 149544 Hom.: 840 Cov.: 0

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.0531

Gnomad AMR AF: 0.0718

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.00137

Gnomad SAS AF: 0.0784

Gnomad FIN AF: 0.0499

Gnomad MID AF: 0.102

Gnomad NFE AF: 0.0886

Gnomad OTH AF: 0.105

GnomAD2 exomes AF: 0.103 AC: 15785 AN: 153394 AF XY: 0.105

Gnomad AFR exome AF: 0.180

Gnomad AMR exome AF: 0.0645

Gnomad ASJ exome AF: 0.151

Gnomad EAS exome AF: 0.00283

Gnomad FIN exome AF: 0.0594

Gnomad NFE exome AF: 0.117

Gnomad OTH exome AF: 0.113

GnomAD4 exome AF: 0.108 AC: 116135 AN: 1074328 Hom.: 5128 AF XY: 0.108 AC XY: 57713 AN XY: 533294

African (AFR) AF: 0.172 AC: 4523 AN: 26340

American (AMR) AF: 0.0710 AC: 1757 AN: 24742

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 2786 AN: 19006

East Asian (EAS) AF: 0.00151 AC: 43 AN: 28412

South Asian (SAS) AF: 0.105 AC: 5578 AN: 52964

European-Finnish (FIN) AF: 0.0626 AC: 2682 AN: 42826

Middle Eastern (MID) AF: 0.134 AC: 619 AN: 4618

European-Non Finnish (NFE) AF: 0.112 AC: 93445 AN: 830746

Other (OTH) AF: 0.105 AC: 4702 AN: 44674

GnomAD4 genome AF: 0.0986 AC: 14758 AN: 149654 Hom.: 843 Cov.: 0 AF XY: 0.0965 AC XY: 7046 AN XY: 73024

African (AFR) AF: 0.151 AC: 6152 AN: 40786

American (AMR) AF: 0.0716 AC: 1073 AN: 14988

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 397 AN: 3434

East Asian (EAS) AF: 0.00137 AC: 7 AN: 5098

South Asian (SAS) AF: 0.0785 AC: 371 AN: 4726

European-Finnish (FIN) AF: 0.0499 AC: 497 AN: 9962

Middle Eastern (MID) AF: 0.103 AC: 30 AN: 292

European-Non Finnish (NFE) AF: 0.0886 AC: 5969 AN: 67392

Other (OTH) AF: 0.103 AC: 214 AN: 2072

Alfa AF: 0.0856 Hom.: 3816

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11292337; hg19: chr2-196756535;