Genetic Variant NM_001394928.1:c.60C>G (chr2-172427848-C-G) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_001394928.1(ITGA6):c.60C>G(p.Leu20Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L20L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ITGA6
NM_001394928.1 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.205

Publications

0 publications found

Variant links:

Genes affected

ITGA6 (HGNC:6142): (integrin subunit alpha 6) The gene encodes a member of the integrin alpha chain family of proteins. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain that function in cell surface adhesion and signaling. The encoded preproprotein is proteolytically processed to generate light and heavy chains that comprise the alpha 6 subunit. This subunit may associate with a beta 1 or beta 4 subunit to form an integrin that interacts with extracellular matrix proteins including members of the laminin family. The alpha 6 beta 4 integrin may promote tumorigenesis, while the alpha 6 beta 1 integrin may negatively regulate erbB2/HER2 signaling. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

ITGA6 Gene-Disease associations (from GenCC):

junctional epidermolysis bullosa with pyloric atresia
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae)
epidermolysis bullosa, junctional 6, with pyloric atresia
Inheritance: AD Classification: LIMITED Submitted by: G2P

ITGA6 links:

ENSG00000226963 (HGNC:):

ENSG00000226963 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP7

Synonymous conserved (PhyloP=-0.205 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394928.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ITGA6	NM_001394928.1	MANE Plus Clinical	c.60C>G	p.Leu20Leu	synonymous	Exon 1 of 26	NP_001381857.1	P23229-1
ITGA6	NM_000210.4	MANE Select	c.60C>G	p.Leu20Leu	synonymous	Exon 1 of 26	NP_000201.2	P23229-2
ITGA6	NM_001079818.3		c.60C>G	p.Leu20Leu	synonymous	Exon 1 of 25	NP_001073286.1	P23229-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ITGA6	ENST00000442250.6	TSL:5 MANE Plus Clinical	c.60C>G	p.Leu20Leu	synonymous	Exon 1 of 26	ENSP00000406694.1	P23229-1
ITGA6	ENST00000684293.1	MANE Select	c.60C>G	p.Leu20Leu	synonymous	Exon 1 of 26	ENSP00000508249.1	P23229-2
ITGA6	ENST00000264107.12	TSL:1	c.60C>G	p.Leu20Leu	synonymous	Exon 1 of 26	ENSP00000264107.8	A0A8C8KBL6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1454060

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723314

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32884

American (AMR)

AF:

0.00

AC:

AN:

43770

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25980

East Asian (EAS)

AF:

0.00

AC:

AN:

39086

South Asian (SAS)

AF:

0.00

AC:

AN:

85250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52224

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

9.02e-7

AC:

AN:

1109024

Other (OTH)

AF:

0.00

AC:

AN:

60090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

8.3

(source)

DANN

Benign

0.44

PhyloP100

-0.20

PromoterAI

-0.012

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over