chr2-195891811-GA-G

Variant names:

• chr2-195891811-GA-G
• rs11292337
• NM_018897.3:c.4897-8delT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_018897.3(DNAH7):​c.4897-8delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.82 (51349 hom., cov: 0)
  • Exomes 𝑓: 0.79 (326764 hom.)
• Consequence: DNAH7 NM_018897.3 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.171
• 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), ClinGen
• 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 -10 ACMG points.

• BP6: Variant 2-195891811-GA-G is Benign according to our data. Variant chr2-195891811-GA-G is described in ClinVar as Benign. ClinVar VariationId is 402751.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018897.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH7	NM_018897.3	MANE Select	c.4897-8delT		splice_region intron	N/A	NP_061720.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH7	ENST00000312428.11	TSL:1 MANE Select	c.4897-8delT		splice_region intron	N/A	ENSP00000311273.6

Frequencies

GnomAD3 genomes AF: 0.820 AC: 122544 AN: 149490 Hom.: 51322 Cov.: 0

Gnomad AFR AF: 0.623

Gnomad AMI AF: 0.947

Gnomad AMR AF: 0.893

Gnomad ASJ AF: 0.859

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.913

Gnomad FIN AF: 0.935

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.881

Gnomad OTH AF: 0.837

GnomAD2 exomes AF: 0.810 AC: 124283 AN: 153394 AF XY: 0.811

Gnomad AFR exome AF: 0.576

Gnomad AMR exome AF: 0.848

Gnomad ASJ exome AF: 0.765

Gnomad EAS exome AF: 0.927

Gnomad FIN exome AF: 0.898

Gnomad NFE exome AF: 0.805

Gnomad OTH exome AF: 0.810

GnomAD4 exome AF: 0.793 AC: 853646 AN: 1075898 Hom.: 326764 Cov.: 0 AF XY: 0.795 AC XY: 424464 AN XY: 534044

African (AFR) AF: 0.551 AC: 14463 AN: 26248

American (AMR) AF: 0.835 AC: 20766 AN: 24866

Ashkenazi Jewish (ASJ) AF: 0.768 AC: 14612 AN: 19030

East Asian (EAS) AF: 0.920 AC: 26221 AN: 28488

South Asian (SAS) AF: 0.808 AC: 42954 AN: 53176

European-Finnish (FIN) AF: 0.875 AC: 37523 AN: 42906

Middle Eastern (MID) AF: 0.815 AC: 3774 AN: 4628

European-Non Finnish (NFE) AF: 0.791 AC: 657846 AN: 831822

Other (OTH) AF: 0.793 AC: 35487 AN: 44734

GnomAD4 genome AF: 0.820 AC: 122617 AN: 149600 Hom.: 51349 Cov.: 0 AF XY: 0.825 AC XY: 60232 AN XY: 72996

African (AFR) AF: 0.623 AC: 25414 AN: 40772

American (AMR) AF: 0.893 AC: 13374 AN: 14976

Ashkenazi Jewish (ASJ) AF: 0.859 AC: 2947 AN: 3432

East Asian (EAS) AF: 0.995 AC: 5076 AN: 5100

South Asian (SAS) AF: 0.913 AC: 4311 AN: 4724

European-Finnish (FIN) AF: 0.935 AC: 9310 AN: 9956

Middle Eastern (MID) AF: 0.890 AC: 260 AN: 292

European-Non Finnish (NFE) AF: 0.881 AC: 59335 AN: 67378

Other (OTH) AF: 0.839 AC: 1734 AN: 2066

Alfa AF: 0.801 Hom.: 3816

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.17
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;