rs2722371

Variant names:

• chr7-37850479-G-A
• rs2722371
• NM_016616.5:c.91+44G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-37850479-G-A
• chr7-37850479-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_016616.5(NME8):​c.91+44G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 1,606,318 control chromosomes in the GnomAD database, including 50,136 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6012 hom., cov: 32)
  • Exomes 𝑓: 0.24 (44124 hom.)
• Consequence: NME8 NM_016616.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.118
• Publications: 8 publications found

Genes affected

NME8 (HGNC:16473): (NME/NM23 family member 8) This gene encodes a protein with an N-terminal thioredoxin domain and three C-terminal nucleoside diphosphate kinase (NDK) domains, but the NDK domains are thought to be catalytically inactive. The sea urchin ortholog of this gene encodes a component of sperm outer dynein arms, and the protein is implicated in ciliary function. Mutations in this gene are implicated in primary ciliary dyskinesia type 6.[provided by RefSeq, Nov 2009]

NME8 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• primary ciliary dyskinesia 6

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen, PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics

ENSG00000290149 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BP6: Variant 7-37850479-G-A is Benign according to our data. Variant chr7-37850479-G-A is described in ClinVar as Benign. ClinVar VariationId is 260770.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NME8	NM_016616.5	c.91+44G>A		intron_variant	Intron 4 of 17	ENST00000199447.9	NP_057700.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NME8	ENST00000199447.9	c.91+44G>A		intron_variant	Intron 4 of 17	1	NM_016616.5	ENSP00000199447.4
ENSG00000290149	ENST00000476620.1	c.-109-6795G>A		intron_variant	Intron 1 of 3	4		ENSP00000425858.1

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41820 AN: 151976 Hom.: 6001 Cov.: 32

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.283

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.258

GnomAD2 exomes AF: 0.230 AC: 57508 AN: 250452 AF XY: 0.224

Gnomad AFR exome AF: 0.375

Gnomad AMR exome AF: 0.203

Gnomad ASJ exome AF: 0.282

Gnomad EAS exome AF: 0.185

Gnomad FIN exome AF: 0.236

Gnomad NFE exome AF: 0.243

Gnomad OTH exome AF: 0.236

GnomAD4 exome AF: 0.242 AC: 352597 AN: 1454226 Hom.: 44124 Cov.: 29 AF XY: 0.240 AC XY: 173444 AN XY: 723934

African (AFR) AF: 0.371 AC: 12364 AN: 33318

American (AMR) AF: 0.207 AC: 9244 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 7354 AN: 26092

East Asian (EAS) AF: 0.183 AC: 7245 AN: 39616

South Asian (SAS) AF: 0.139 AC: 11930 AN: 86094

European-Finnish (FIN) AF: 0.235 AC: 12564 AN: 53382

Middle Eastern (MID) AF: 0.239 AC: 1355 AN: 5664

European-Non Finnish (NFE) AF: 0.250 AC: 275906 AN: 1105220

Other (OTH) AF: 0.243 AC: 14635 AN: 60128

GnomAD4 genome AF: 0.275 AC: 41863 AN: 152092 Hom.: 6012 Cov.: 32 AF XY: 0.272 AC XY: 20229 AN XY: 74338

African (AFR) AF: 0.366 AC: 15169 AN: 41480

American (AMR) AF: 0.250 AC: 3814 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 972 AN: 3468

East Asian (EAS) AF: 0.180 AC: 927 AN: 5162

South Asian (SAS) AF: 0.137 AC: 659 AN: 4826

European-Finnish (FIN) AF: 0.246 AC: 2601 AN: 10570

Middle Eastern (MID) AF: 0.291 AC: 85 AN: 292

European-Non Finnish (NFE) AF: 0.249 AC: 16949 AN: 68006

Other (OTH) AF: 0.257 AC: 543 AN: 2110

Alfa AF: 0.257 Hom.: 13306

Bravo AF: 0.277

Asia WGS AF: 0.164 AC: 571 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.67
DANN	Benign	0.33
PhyloP100		-0.12
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: rs2722371; hg19: chr7-37890081; COSMIC: COSV52250741;