Genetic Variant ITM2A:c.442-10T>C (chrX-79362701-A-G) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_004867.5(ITM2A):c.442-10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00065 in 1,120,976 control chromosomes in the GnomAD database, including 4 homozygotes. There are 196 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0031 ( 1 hom., 106 hem., cov: 22)

Exomes 𝑓: 0.00039 ( 3 hom. 90 hem. )

Consequence

ITM2A
NM_004867.5 intron

Scores

Splicing: ADA: 0.0002121

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.54

Variant links:

Genes affected

ITM2A (HGNC:6173): (integral membrane protein 2A) This gene encodes a type II membrane protein that belongs to the ITM2 family. Studies in mouse suggest that it may be involved in osteo- and chondrogenic differentiation. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2010]

ITM2A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant X-79362701-A-G is Benign according to our data. Variant chrX-79362701-A-G is described in ClinVar as [Benign]. Clinvar id is 714929.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Hemizygotes in GnomAd4 at 106 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITM2A	NM_004867.5 link	c.442-10T>C		intron_variant	Intron 3 of 5	ENST00000373298.7	NP_004858.1	O43736-1
ITM2A	NM_001171581.2 link	c.310-10T>C		intron_variant	Intron 2 of 4		NP_001165052.1	O43736-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ITM2A	ENST00000373298.7 link	c.442-10T>C	intron_variant	Intron 3 of 5	1	NM_004867.5	ENSP00000362395.2	O43736-1
ITM2A	ENST00000434584.2 link	c.310-10T>C	intron_variant	Intron 2 of 4	2		ENSP00000415533.2	O43736-2
ITM2A	ENST00000469541.5 link	n.402-10T>C	intron_variant	Intron 3 of 5	2
ITM2A	ENST00000482194.1 link	n.413-10T>C	intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.00306

AC:

340

AN:

111101

Hom.:

Cov.:

AF XY:

0.00318

AC XY:

106

AN XY:

33289

show subpopulations

Gnomad AFR

AF:

0.0106

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00106

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000754

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00111

AC:

187

AN:

167723

Hom.:

AF XY:

0.000808

AC XY:

AN XY:

56947

show subpopulations

Gnomad AFR exome

AF:

0.0126

Gnomad AMR exome

AF:

0.000558

Gnomad ASJ exome

AF:

0.000156

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000645

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000909

Gnomad OTH exome

AF:

0.000488

GnomAD4 exome

AF:

0.000385

AC:

389

AN:

1009823

Hom.:

Cov.:

AF XY:

0.000311

AC XY:

AN XY:

289831

show subpopulations

Gnomad4 AFR exome

AF:

0.0121

Gnomad4 AMR exome

AF:

0.000782

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000202

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000208

Gnomad4 OTH exome

AF:

0.000973

GnomAD4 genome

AF:

0.00306

AC:

340

AN:

111153

Hom.:

Cov.:

AF XY:

0.00318

AC XY:

106

AN XY:

33351

show subpopulations

Gnomad4 AFR

AF:

0.0106

Gnomad4 AMR

AF:

0.00106

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000754

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00139

Hom.:

Bravo

AF:

0.00428

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

8.9

DANN

Benign

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00021

dbscSNV1_RF

Benign

0.052

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over